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29,075,572
|
Reflex-based grasping, skilled forelimb reaching, and electrodiagnostic evaluation for comprehensive analysis of functional recovery-The 7-mm rat median nerve gap repair model revisited.
|
The rat median nerve injury and repair model gets increasingly important for research on novel bioartificial nerve grafts. It allows follow-up evaluation of the recovery of the forepaw functional ability with several sensitive techniques. The reflex-based grasping test, the skilled forelimb reaching staircase test, as well as electrodiagnostic recordings have been described useful in this context. Currently, no standard values exist, however, for comparison or comprehensive correlation of results obtained in each of the three methods after nerve gap repair in adult rats.
|
Brain and behavior
| 2,017
| 10
| 3
| 20
|
30,171,365
|
Effect of exogenous estrogens and progestogens on the course of migraine during reproductive age: a consensus statement by the European Headache Federation (EHF) and the European Society of Contraception and Reproductive Health (ESCRH).
|
We systematically reviewed data about the effect of exogenous estrogens and progestogens on the course of migraine during reproductive age. Thereafter a consensus procedure among international experts was undertaken to develop statements to support clinical decision making, in terms of possible effects on migraine course of exogenous estrogens and progestogens and on possible treatment of headache associated with the use or with the withdrawal of hormones. Overall, quality of current evidence is low. Recommendations are provided for all the compounds with available evidence including the conventional 21/7 combined hormonal contraception, the desogestrel only oral pill, combined oral contraceptives with shortened pill-free interval, combined oral contraceptives with estradiol supplementation during the pill-free interval, extended regimen of combined hormonal contraceptive with pill or patch, combined hormonal contraceptive vaginal ring, transdermal estradiol supplementation with gel, transdermal estradiol supplementation with patch, subcutaneous estrogen implant with cyclical oral progestogen. As the quality of available data is poor, further research is needed on this topic to improve the knowledge about the use of estrogens and progestogens in women with migraine. There is a need for better management of headaches related to the use of hormones or their withdrawal.
|
The journal of headache and pain
| 2,018
| 8
| 6
| 54
|
26,627,247
|
Responsiveness of G protein-coupled odorant receptors is partially attributed to the activation mechanism.
|
Mammals detect and discriminate numerous odors via a large family of G protein-coupled odorant receptors (ORs). However, little is known about the molecular and structural basis underlying OR response properties. Using site-directed mutagenesis and computational modeling, we studied ORs sharing high sequence homology but with different response properties. When tested in heterologous cells by diverse odorants, MOR256-3 responded broadly to many odorants, whereas MOR256-8 responded weakly to a few odorants. Out of 36 mutant MOR256-3 ORs, the majority altered the responses to different odorants in a similar manner and the overall response of an OR was positively correlated with its basal activity, an indication of ligand-independent receptor activation. Strikingly, a single mutation in MOR256-8 was sufficient to confer both high basal activity and broad responsiveness to this receptor. These results suggest that broad responsiveness of an OR is at least partially attributed to its activation likelihood.
|
Proceedings of the National Academy of Sciences of the United States of America
| 2,015
| 12
| 3
| 33
|
19,210,000
|
Synesthesia: a new approach to understanding the development of perception.
|
In this article, the authors introduce a new theoretical framework for understanding intersensory development. Their approach is based upon insights gained from adults who experience synesthesia, in whom sensory stimuli induce extra cross-modal or intramodal percepts. Synesthesia appears to represent one way that typical developmental mechanisms can play out by magnifying connections present in early life that are pruned and/or inhibited during development but persist in muted form in all adults. As such, the study of synesthesia provides valuable insights into the nature of intersensory development. The authors review evidence on the perceptual reality and neural basis of synesthesia, then summarize developmental models and evidence that its underlying mechanisms are universal in adults. They illustrate how evidence for consistent sensory associations in adults leads to predictions about toddlers' perception and present 3 bodies of work that have confirmed those hypotheses. They end by describing novel hypotheses about intersensory development that arise from this framework. Such intersensory associations appear to reflect intrinsic sensory cortical organization that influences the development of perception and of language and that may constrain the learning of environmentally based associations.
|
Developmental psychology
| 2,009
| 1
| 3
| 47
|
20,730,435
|
Active wall following by Mexican blind cavefish (Astyanax mexicanus).
|
When introduced into a novel environment that limits or prevents vision, a variety of species including Mexican blind cavefish (Astyanax mexicanus) exhibit wall-following behaviors. It is often assumed that wall following serves an exploratory function, but this assertion remains untested against alternative artifactual explanations. Here, we test whether wall following by cavefish is a purposeful behavior in which fish actively maintain a close relationship with the wall, or an artifactual consequence of being enclosed in a small concave arena, in which fish turn slightly to avoid the wall whenever it impedes forward movement. Wall-following abilities of fish were tested in a large, goggle-shaped arena, where forward motion along the convex wall was unimpeded. In this circumstance, cavefish continued to follow the wall at frequencies significantly above chance levels. Lateral line inactivation significantly reduced the ability of fish to follow convex, but not concave or straight, walls. Wall-following abilities of normal fish decreased with decreasing radius of wall convex curvature. Our results demonstrate that cavefish actively follow walls of varying contours. Radius-of-curvature effects coupled with the difficulties posed by convex walls to lateral line-deprived fish suggest a partially complementary use of tactile and lateral line information to regulate distance from the wall.
|
Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology
| 2,010
| 11
| 2
| 21
|
30,817,854
|
SLC35A2-CDG: Functional characterization, expanded molecular, clinical, and biochemical phenotypes of 30 unreported Individuals.
|
Pathogenic de novo variants in the X-linked gene SLC35A2 encoding the major Golgi-localized UDP-galactose transporter required for proper protein and lipid glycosylation cause a rare type of congenital disorder of glycosylation known as SLC35A2-congenital disorders of glycosylation (CDG; formerly CDG-IIm). To date, 29 unique de novo variants from 32 unrelated individuals have been described in the literature. The majority of affected individuals are primarily characterized by varying degrees of neurological impairments with or without skeletal abnormalities. Surprisingly, most affected individuals do not show abnormalities in serum transferrin N-glycosylation, a common biomarker for most types of CDG. Here we present data characterizing 30 individuals and add 26 new variants, the single largest study involving SLC35A2-CDG. The great majority of these individuals had normal transferrin glycosylation. In addition, expanding the molecular and clinical spectrum of this rare disorder, we developed a robust and reliable biochemical assay to assess SLC35A2-dependent UDP-galactose transport activity in primary fibroblasts. Finally, we show that transport activity is directly correlated to the ratio of wild-type to mutant alleles in fibroblasts from affected individuals.
|
Human mutation
| 2,019
| 7
| 6
| 35
|
23,521,808
|
Manipulating the sleep-wake cycle and circadian rhythms to improve clinical management of major depression.
|
Clinical psychiatry has always been limited by the lack of objective tests to substantiate diagnoses and a lack of specific treatments that target underlying pathophysiology. One area in which these twin failures has been most frustrating is major depression. Due to very considerable progress in the basic and clinical neurosciences of sleep-wake cycles and underlying circadian systems this situation is now rapidly changing.
|
BMC medicine
| 2,013
| 3
| 4
| 35
|
24,643,313
|
Effect of a family intervention on psychological outcomes of children affected by parental HIV.
|
This study assesses intervention outcomes in children's self-esteem, perceived parental care, and problem behavior and their potential connections to intervention outcomes in depressive symptoms and family functioning reported by parents living with HIV (PLH) and family members. A total of 79 families were recruited from Anhui province, China. The intervention was delivered at the individual, family and community levels. Face-to-face interviews were administered at baseline, 3 and 6 months. A mixed-effects regression model was used to assess the intervention effect on the improvement of children's reported self-esteem, parental care, and problem behavior. To further investigate the association between the parental measures and their children's outcomes, we added parental measure as a time-varying covariate to explore whether the intervention effect on children was influenced by the parental measures. We observed some intervention effects related to children's psychological measures accompanied by the improvement in mental health of PLH and family members. Our study findings highlight the importance of empowering families as a whole to confront HIV related challenges and the need to develop child-adequate and age-specific intervention strategies.
|
AIDS and behavior
| 2,014
| 11
| 2
| 9
|
26,459,092
|
Autosomal dominant epilepsy with auditory features: a new LGI1 family including a phenocopy with cortical dysplasia.
|
We report a new family with autosomal dominant epilepsy with auditory features (ADEAF) including focal cortical dysplasia (FCD) in the proband. We aim to identify the molecular cause in this family and clarify the relationship between FCD and ADEAF. A large Iranian Jewish family including 14 individuals with epileptic seizures was phenotyped including high-resolution 3-T MRI. We performed linkage analysis and exome sequencing. LGI1, KANK1 and RELN were Sanger sequenced. Seizure semiology of 11 individuals was consistent with ADEAF. The proband underwent surgery for right mesiotemporal FCD. 3-T MRIs in four individuals were unremarkable. Linkage analysis revealed peaks on chromosome 9p24 (LOD 2.43) and 10q22-25 (LOD 2.04). A novel heterozygous LGI1 mutation was identified in all affected individuals except for the proband indicating a phenocopy. Exome sequencing did not reveal variants within the chromosome 9p24 region. Closely located variants in KANK1 and a RELN variant did not segregate with the phenotype. We provide detailed description of the phenotypic spectrum within a large ADEAF family with a novel LGI1 mutation that was conspicuously absent in the proband with FCD, demonstrating that despite identical clinical symptoms, phenocopies in ADEAF families may exist. This family illustrates that rare epilepsy syndromes within a single family can have both genetic and structural etiologies.
|
Journal of neurology
| 2,016
| 1
| 1
| 7
|
25,522,415
|
Treatment implications of predominant polarity and the polarity index: a comprehensive review.
|
Bipolar disorder (BD) is a serious and recurring condition that affects approximately 2.4% of the global population. About half of BD sufferers have an illness course characterized by either a manic or a depressive predominance. This predominant polarity in BD may be differentially associated with several clinical correlates. The concept of a polarity index (PI) has been recently proposed as an index of the antimanic versus antidepressive efficacy of various maintenance treatments for BD. Notwithstanding its potential clinical utility, predominant polarity was not included in the DSM-5 as a BD course specifier.
|
The international journal of neuropsychopharmacology
| 2,014
| 10
| 2
| 18
|
25,934,490
|
Transcranial direct current stimulation (tDCS) of frontal cortex decreases performance on the WAIS-IV intelligence test.
|
Transcranial direct current stimulation (tDCS) modulates excitability of motor cortex. However, there is conflicting evidence about the efficacy of this non-invasive brain stimulation modality to modulate performance on cognitive tasks. Previous work has tested the effect of tDCS on specific facets of cognition and executive processing. However, no randomized, double-blind, sham-controlled study has looked at the effects of tDCS on a comprehensive battery of cognitive processes. The objective of this study was to test if tDCS had an effect on performance on a comprehensive assay of cognitive processes, a standardized intelligence quotient (IQ) test. The study consisted of two substudies and followed a double-blind, between-subjects, sham-controlled design. In total, 41 healthy adult participants were included in the final analysis. These participants completed the Wechsler Adult Intelligence Scale, Fourth Edition (WAIS-IV) as a baseline measure. At least one week later, participants in substudy 1 received either bilateral tDCS (anodes over both F4 and F3, cathode over Cz, 2 mA at each anode for 20 min) or active sham tDCS (2 mA for 40 s), and participants in substudy 2 received either right or left tDCS (anode over either F4 or F3, cathode over Cz, 2 mA for 20 min). In both studies, the WAIS-IV was immediately administered following stimulation to assess for performance differences induced by bilateral and unilateral tDCS. Compared to sham stimulation, right, left, and bilateral tDCS reduced improvement between sessions on Full Scale IQ and the Perceptual Reasoning Index. This demonstration that frontal tDCS selectively degraded improvement on specific metrics of the WAIS-IV raises important questions about the often proposed role of tDCS in cognitive enhancement.
|
Behavioural brain research
| 2,015
| 9
| 9
| 38
|
22,889,311
|
Effects of muscimol in the nucleus accumbens shell on salt appetite and sucrose intake: a microstructural study with a comment on the sensitization of salt intake.
|
Previous work has demonstrated that injections of the γ-aminobutyric acidA (GABAA) agonist muscimol into the nucleus accumbens shell (AcbSh) induce pronounced increases in the intake of solid foods and sucrose solutions, but do not potentiate water intake. In order to clarify the range of situations in which inactivation of the AcbSh potentiates ingestive behavior, we examined the effects of muscimol injections on the intake of a 3% NaCl solution in sodium-depleted animals. Although sodium-depleted subjects avidly consumed this solution, muscimol injections had no effect either on the volume consumed or on a variety of microstructural licking parameters. In contrast, in these same animals, muscimol injections significantly increased licking of a 10% sucrose solution. These results suggest that inactivation of the AcbSh may selectively increase the intake of foods, but not that of other homeostatically relevant ingestates. Examination of microstructural parameters suggested that the effect of muscimol on sucrose intake was not mediated by alterations in the "palatability" of the sucrose solution. We also observed that sodium-depleted subjects displayed significantly larger salt intakes after their second experience with sodium depletion than their first, and microstructural analysis in this case indicated that this sensitization effect was produced in a manner consistent with the animals showing increased "hedonic responsiveness" to the salt solution.
|
Behavioral neuroscience
| 2,012
| 10
| 0
| 5
|
30,299,280
|
Pathophysiology of Placenta Accreta Spectrum Disorders: A Review of Current Findings.
|
Current findings continue to support the concept of a biologically defective decidua rather than a primarily abnormally invasive trophoblast. Prior cesarean sections increase the risk of placenta previa and both adherent and invasive placenta accreta, suggesting that the endometrial/decidual defect following the iatrogenic creation of a uterine myometrium scar has an adverse effect on early implantation. Preferential attachment of the blastocyst to scar tissue facilitates abnormally deep invasion of trophoblastic cells and interactions with the radial and arcuate arteries. Subsequent high velocity maternal arterial inflow into the placenta creates large lacunae, destroying the normal cotyledonary arrangement of the villi.
|
Clinical obstetrics and gynecology
| 2,018
| 12
| 4
| 61
|
28,879,438
|
Do cognition and other non-motor symptoms decline similarly among patients with Parkinson's disease motor subtypes? Findings from a 5-year prospective study.
|
Among patients with Parkinson's disease (PD), a wide range of motor and non-motor symptoms (NMS) are evident. PD is often divided into tremor dominant (TD) and postural instability gait difficulty (PIGD) motor subtypes. We evaluated the effect of disease duration and aimed to characterize whether there are differences in the deterioration of cognitive function and other NMS between the PIGD and TD subtypes. Sixty-three subjects were re-evaluated at the follow-up visit about 5 years after baseline examination. Cognitive function and other NMS were assessed. At follow-up, the PIGD and TD groups were similar with respect to medications, comorbidities and disease-related symptoms. There was a significant time effect for all measures, indicating deterioration and worsening in both groups. However, cognitive scores, particularly those related to executive function, became significantly worse in the PIGD with a more moderate decrease in the TD group. For example, the computerized global cognitive score declined in the PIGD group from 94.21 ± 11.88 to 83.91 ± 13.76, p < 0.001. This decline was significantly larger (p = 0.03) than the decrease observed in the TD group (96.56 ± 10.29 to 92.21 ± 14.20, p = 0.047). A significant group × time interaction effect was found for the change in global cognitive score (p = 0.047), the executive function index (p = 0.002) and accuracy on a motor-cognitive catch game (p = 0.008). In contrast, several NMS including depression, health-related quality of life and fear of falling deteriorated in parallel in both subtypes, with no interaction effect. The present findings highlight the difference in the natural history of the disease between the two PD "motor" subtypes. While the PIGD group demonstrated a significant cognitive decline, especially in executive functions, a more favorable course was observed in the TD subtype. This behavior was not seen in regards to the other NMS.
|
Journal of neurology
| 2,017
| 10
| 1
| 29
|
27,898,091
|
Restoring Ureagenesis in Hepatocytes by CRISPR/Cas9-mediated Genomic Addition to Arginase-deficient Induced Pluripotent Stem Cells.
|
Urea cycle disorders are incurable enzymopathies that affect nitrogen metabolism and typically lead to hyperammonemia. Arginase deficiency results from a mutation in Arg1, the enzyme regulating the final step of ureagenesis and typically results in developmental disabilities, seizures, spastic diplegia, and sometimes death. Current medical treatments for urea cycle disorders are only marginally effective, and for proximal disorders, liver transplantation is effective but limited by graft availability. Advances in human induced pluripotent stem cell research has allowed for the genetic modification of stem cells for potential cellular replacement therapies. In this study, we demonstrate a universally-applicable CRISPR/Cas9-based strategy utilizing exon 1 of the hypoxanthine-guanine phosphoribosyltransferase locus to genetically modify and restore arginase activity, and thus ureagenesis, in genetically distinct patient-specific human induced pluripotent stem cells and hepatocyte-like derivatives. Successful strategies restoring gene function in patient-specific human induced pluripotent stem cells may advance applications of genetically modified cell therapy to treat urea cycle and other inborn errors of metabolism.
|
Molecular therapy. Nucleic acids
| 2,016
| 11
| 4
| 21
|
29,328,926
|
DNA damage-associated oligodendrocyte degeneration precedes amyloid pathology and contributes to Alzheimer's disease and dementia.
|
In looking for novel non-amyloid-based etiologies for Alzheimer's disease, we explore the hypothesis that age-related myelin loss is an attractive explanation for age-associated cognitive decline and dementia.
|
Alzheimer's & dementia : the journal of the Alzheimer's Association
| 2,018
| 5
| 1
| 29
|
24,630,282
|
Long-term neurocognitive outcome and quality of life in pediatric acute disseminated encephalomyelitis.
|
Acute disseminated encephalomyelitis is an inflammatory-demyelinating disorder of the central nervous system usually with a monophasic course and a favorable neurological outcome. Long-term neurocognitive sequelae and quality of life have not yet been fully investigated.
|
Pediatric neurology
| 2,014
| 4
| 1
| 21
|
22,197,833
|
Chromatin modification of Notch targets in olfactory receptor neuron diversification.
|
Neuronal-class diversification is central during neurogenesis. This requirement is exemplified in the olfactory system, which utilizes a large array of olfactory receptor neuron (ORN) classes. We discovered an epigenetic mechanism in which neuron diversity is maximized via locus-specific chromatin modifications that generate context-dependent responses from a single, generally used intracellular signal. Each ORN in Drosophila acquires one of three basic identities defined by the compound outcome of three iterated Notch signaling events during neurogenesis. Hamlet, the Drosophila Evi1 and Prdm16 proto-oncogene homolog, modifies cellular responses to these iteratively used Notch signals in a context-dependent manner, and controls odorant receptor gene choice and ORN axon targeting specificity. In nascent ORNs, Hamlet erases the Notch state inherited from the parental cell, enabling a modified response in a subsequent round of Notch signaling. Hamlet directs locus-specific modifications of histone methylation and histone density and controls accessibility of the DNA-binding protein Suppressor of Hairless at the Notch target promoter.
|
Nature neuroscience
| 2,011
| 12
| 6
| 43
|
27,466,334
|
mGluR1 and mGluR5 Synergistically Control Cholinergic Synaptic Transmission in the Thalamic Reticular Nucleus.
|
Acetylcholine (ACh) signaling is involved in a wide range of processes, including arousal, attention, and learning. An increasing number of studies indicate that cholinergic control of these functions is highly deterministic, mediated by synaptic afferents that generate reliable and precise responses in postsynaptic neurons. However, mechanisms that govern plastic changes of cholinergic synaptic strength are poorly understood, even though they are likely critical in shaping the impact of cholinergic inputs on neuronal networks. We have recently shown that in the thalamic reticular nucleus (TRN), synaptic release of ACh generates excitatory-inhibitory biphasic postsynaptic responses, mediated by the activation of α4β2 nicotinic (nAChRs) and M2 muscarinic receptors (mAChRs), respectively. Here, using voltage-clamp recordings from TRN neurons in thalamocortical slices of mice, we demonstrate that the activation of Group I metabotropic glutamate receptors (mGluRs) by ambient or synaptically released glutamate evokes transient increases of nicotinic EPSCs. Additionally, we find that the selective Group I mGluR agonist DHPG [(S)-3,5-dihydroxyphenylglycine] evokes long-term potentiation of nicotinic EPSCs (mGluR-nLTP), dependent on increases in postsynaptic Ca(2+) concentration and the activation of phospholipase C. Both the induction and the maintenance of mGluR-nLTP require synergistic activation of mGluR1 and mGluR5. Together, our results show that postsynaptic Group I mGluRs are critically involved in the regulation of cholinergic synaptic strength on different time scales, suggesting that cholinergic control of local thalamic circuits is highly context-dependent and regulated by the overall levels of glutamatergic afferent activity.
|
The Journal of neuroscience : the official journal of the Society for Neuroscience
| 2,016
| 7
| 1
| 11
|
25,486,177
|
Analysis of motor function in 6-month-old male and female 3xTg-AD mice.
|
The 3xTg-AD mouse has high validity as a model of Alzheimer's disease (AD) because it develops both amyloid beta plaques and neurofibrillary tangles. Human patients with AD typically develop motor deficits, which worsen as the disease progresses, but 3xTg-AD mice have been reported to show enhanced motor abilities. We investigated the motor behaviour phenotype of male and female 3xTg-AD and B6129SF2 wildtype mice on a battery of motor behaviours at 6 months of age. Compared to wildtype mice, the 3xTg-AD mice had enhanced motor performance on the Rotarod, but worse performance on the grid suspension task. In gait analysis 3xTg-AD mice had a longer stride length and made more foot slips on the balance beam than wildtype mice. There was no overall difference in voluntary wheel-running activity between genotypes, but there was a disruption in circadian activity rhythm in 3xTg-AD mice. In some motor tasks, such as the Rotarod and balance beam, females appeared to perform better than males, but this sex differences was accounted for by differences in body weight. Our results indicate that while the 3xTg-AD mice show enhanced performance on the Rotarod, they have poorer performance on other motor behaviour tasks, indicating that their motor behaviour phenotype is more complex than previously reported. The presence of the P301L transgene may explain the enhancement of Rotarod performance but the poorer performance on other motor behaviour tasks may be due to other transgenes.
|
Behavioural brain research
| 2,015
| 3
| 2
| 32
|
22,361,232
|
Contributions of central and systemic inflammation to the pathophysiology of Parkinson's disease.
|
Idiopathic Parkinson's disease (PD) represents a complex interaction between the inherent vulnerability of the nigrostriatal dopaminergic system, a possible genetic predisposition, and exposure to environmental toxins including inflammatory triggers. Evidence now suggests that chronic neuroinflammation is consistently associated with the pathophysiology of PD. Activation of microglia and increased levels of pro-inflammatory mediators such as TNF-α, IL-1β and IL-6, reactive oxygen species and eicosanoids has been reported after post-mortem analysis of the substantia nigra from PD patients and in animal models of PD. It is hypothesised that chronically activated microglia secrete high levels of pro-inflammatory mediators which damage neurons and further activate microglia, resulting in a feed forward cycle promoting further inflammation and neurodegeneration. Moreover, nigrostriatal dopaminergic neurons are more vulnerable to pro-inflammatory and oxidative mediators than other cell types because of their low intracellular glutathione concentration. Systemic inflammation has also been suggested to contribute to neurodegeneration in PD, as lymphocyte infiltration has been observed in brains of PD patients and in animal models of PD, substantiating the current theory of a fundamental role of inflammation in neurodegeneration. We will examine the current evidence in the literature which offers insight into the premise that both central and systemic inflammation may contribute to neurodegeneration in PD. We will discuss the emerging possibility of the use of diagnostic tools such as imaging technologies for PD patients. Finally, we will present the immunomodulatory therapeutic strategies that are now under investigation and in clinical trials as potential neuroprotective drugs for PD.
|
Neuropharmacology
| 2,012
| 6
| 12
| 98
|
27,411,012
|
Mitochondrial Biogenesis and Proteome Remodeling Promote One-Carbon Metabolism for T Cell Activation.
|
Naive T cell stimulation activates anabolic metabolism to fuel the transition from quiescence to growth and proliferation. Here we show that naive CD4(+) T cell activation induces a unique program of mitochondrial biogenesis and remodeling. Using mass spectrometry, we quantified protein dynamics during T cell activation. We identified substantial remodeling of the mitochondrial proteome over the first 24 hr of T cell activation to generate mitochondria with a distinct metabolic signature, with one-carbon metabolism as the most induced pathway. Salvage pathways and mitochondrial one-carbon metabolism, fed by serine, contribute to purine and thymidine synthesis to enable T cell proliferation and survival. Genetic inhibition of the mitochondrial serine catabolic enzyme SHMT2 impaired T cell survival in culture and antigen-specific T cell abundance in vivo. Thus, during T cell activation, mitochondrial proteome remodeling generates specialized mitochondria with enhanced one-carbon metabolism that is critical for T cell activation and survival.
|
Cell metabolism
| 2,016
| 7
| 14
| 157
|
21,543,596
|
Recalling and forgetting dreams: theta and alpha oscillations during sleep predict subsequent dream recall.
|
Under the assumption that dream recall is a peculiar form of declarative memory, we have hypothesized that (1) the encoding of dream contents during sleep should share some electrophysiological mechanisms with the encoding of episodic memories of the awake brain and (2) recalling a dream(s) after awakening from non-rapid eye movement (NREM) and rapid eye movement (REM) sleep should be associated with different brain oscillations. Here, we report that cortical brain oscillations of human sleep are predictive of successful dream recall. In particular, after morning awakening from REM sleep, a higher frontal 5-7 Hz (theta) activity was associated with successful dream recall. This finding mirrors the increase in frontal theta activity during successful encoding of episodic memories in wakefulness. Moreover, in keeping with the different EEG background, a different predictive relationship was found after awakening from stage 2 NREM sleep. Specifically, a lower 8-12 Hz (alpha) oscillatory activity of the right temporal area was associated with a successful dream recall. These findings provide the first evidence of univocal cortical electroencephalographic correlates of dream recall, suggesting that the neurophysiological mechanisms underlying the encoding and recall of episodic memories may remain the same across different states of consciousness.
|
The Journal of neuroscience : the official journal of the Society for Neuroscience
| 2,011
| 5
| 6
| 35
|
30,296,688
|
Novel potential pyrazolopyrimidine based translocator protein ligands for the evaluation of neuroinflammation with PET.
|
Translocator protein (TSPO) is an interesting biological target because TSPO overexpression is associated with microglial activation caused by neuronal damage or neuroinflammation, and these activated microglia are involved in several central nervous system diseases. Herein, novel fluorinated ligands (14a-c and 16a-c) based on a 2-phenylpyrazolo[1,5-a]pyrimidin-3-yl acetamide scaffold were synthesized, and in vitro characterization of each of the novel ligands was performed to elucidate structure activity relationships. All of the newly synthesized ligands displayed nano-molar affinity for TSPO. Particularly, an in vitro affinity study suggests that 2-(5,7-diethyl-2-(4-(3-fluoro-2-methylpropoxy)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)-N,N-diethylacetamide (14a), which exhibited high nano-molar affinity for TSPO and proper lipophilicity, was suitable for in vivo brain studies. Thus, radiosynthesis from tosylate precursor 13a using fluorine-18 was performed, and [
|
European journal of medicinal chemistry
| 2,018
| 11
| 1
| 13
|
31,534,222
|
Electrical and synaptic integration of glioma into neural circuits.
|
High-grade gliomas are lethal brain cancers whose progression is robustly regulated by neuronal activity. Activity-regulated release of growth factors promotes glioma growth, but this alone is insufficient to explain the effect that neuronal activity exerts on glioma progression. Here we show that neuron and glioma interactions include electrochemical communication through bona fide AMPA receptor-dependent neuron-glioma synapses. Neuronal activity also evokes non-synaptic activity-dependent potassium currents that are amplified by gap junction-mediated tumour interconnections, forming an electrically coupled network. Depolarization of glioma membranes assessed by in vivo optogenetics promotes proliferation, whereas pharmacologically or genetically blocking electrochemical signalling inhibits the growth of glioma xenografts and extends mouse survival. Emphasizing the positive feedback mechanisms by which gliomas increase neuronal excitability and thus activity-regulated glioma growth, human intraoperative electrocorticography demonstrates increased cortical excitability in the glioma-infiltrated brain. Together, these findings indicate that synaptic and electrical integration into neural circuits promotes glioma progression.
|
Nature
| 2,019
| 9
| 82
| 755
|
21,076,426
|
The columnar and laminar organization of inhibitory connections to neocortical excitatory cells.
|
The cytoarchitectonic similarities of different neocortical regions have given rise to the idea of 'canonical' connectivity between excitatory neurons of different layers within a column. It is unclear whether similarly general organizational principles also exist for inhibitory neocortical circuits. Here we delineate and compare local inhibitory-to-excitatory wiring patterns in all principal layers of primary motor (M1), somatosensory (S1) and visual (V1) cortex, using genetically targeted photostimulation in a mouse knock-in line that conditionally expresses channelrhodopsin-2 in GABAergic neurons. Inhibitory inputs to excitatory neurons derived largely from the same cortical layer within a three-column diameter. However, subsets of pyramidal cells in layers 2/3 and 5B received extensive translaminar inhibition. These neurons were prominent in V1, where they might correspond to complex cells, less numerous in barrel cortex and absent in M1. Although inhibitory connection patterns were stereotypical, the abundance of individual motifs varied between regions and cells, potentially reflecting functional specializations.
|
Nature neuroscience
| 2,011
| 1
| 20
| 93
|
32,128,587
|
Interactional synchrony: signals, mechanisms and benefits.
|
Many group-living animals, humans included, occasionally synchronize their behavior with that of conspecifics. Social psychology and neuroscience have attempted to explain this phenomenon. Here we sought to integrate results around three themes: the stimuli, the mechanisms and the benefits of interactional synchrony. As regards stimuli, we asked what characteristics, apart from temporal regularity, prompt synchronization and found that stimulus modality and complexity are important. The high temporal resolution of the auditory system and the relevance of socio-emotional information endow auditory, multimodal, emotional and somewhat variable and adaptive sequences with particular synchronizing power. Looking at the mechanisms revealed that traditional perspectives emphasizing beat-based representations of others' signals conflict with more recent work investigating the perception of temporal regularity. Timing processes supported by striato-cortical loops represent any kind of repetitive interval sequence fairly automatically. Additionally, socio-emotional processes supported by posterior superior temporal cortex help endow such sequences with value motivating the extent of synchronizing. Synchronizing benefits arise from an increased predictability of incoming signals and include many positive outcomes ranging from basic information processing at the individual level to the bonding of dyads and larger groups.
|
Social cognitive and affective neuroscience
| 2,021
| 1
| 17
| 103
|
28,274,139
|
Immune and viral therapies for malignant primary brain tumors.
|
Glioblastoma multiforme (GBM) is a primary brain tumor with great lethality. Current standard of care with surgery, radiation therapy, and chemotherapy are ineffective in curing this disease. Recent advancements in biological therapies show promise in treating brain tumors. Areas covered: This article provides a review of: the peripheral activation of antigen presenting cells such as dendritic cells to stimulate T cells to recognize and destroy tumor cells within the brain; the ex vivo expansion and transfer of dendritic cells, T cells, and engineered T cells expressing chimeric antigen receptors to target cells bearing specific tumor antigens as well as monoclonal antibodies as immune check point inhibitors. Gene therapy approaches have also been utilized to employ viral vectors in transducing cells to express cytokines for activating immune responses to brain tumors. Finally, the article reviews engineering of viruses for oncolytic targeting and destruction of malignant tumors within the brain. Expert opinion: The ultimate goal of immune and viral approaches for treating malignant brain tumors is to cure this disease. Preclinical and clinical studies utilizing these biological therapeutic approaches for treating brain tumors have the potential to augment the current standard of care to provide potential curative therapies.
|
Expert opinion on biological therapy
| 2,017
| 4
| 5
| 13
|
24,350,870
|
Global stroke statistics.
|
In many countries, stroke is a lower priority than other diseases despite its public health impact. One issue is a lack of readily accessible comparative data to help make the case for the development of national stroke strategies. To assist in this process, we need to have a common repository of the latest published information on the impact of stroke worldwide. We aim to provide a repository of the most current incidence and mortality data on stroke available by country and illustrate the gaps in these data. We plan to update this repository annually and expand the scope to address other aspects of the burden of stroke. Data were compiled using two approaches: (1) an extensive literature review with a major focus on published systematic reviews on stroke incidence (between 1980 and May 14, 2013); and (2) direct acquisition and collation of data from the World Health Organization to present the most current estimates of stroke mortality for each country recognized by the World Health Organization. For mortality, ICD8, ICD9, and ICD10 mortality codes were extracted. Using population denominators crude stroke mortality was calculated, as well as adjusting for the World Health Organization world population. We used only the most recent year reported to the World Health Organization. Incidence rates for stroke were available for 52 countries, with some countries having incidence studies undertaken in more than one region. When adjusted to the World Health Organization world standard population, incidence rates for stroke ranged from 41 per 100 000 population per year in Nigeria (1971-74) to 316/ 100 000/year in urban Dar-es-Salaam (Tanzania). Some regions had three to fivefold greater incidence than other countries. Of the 123 countries reporting mortality data, crude mortality was greatest in Kazhakstan (in 2003). In many regions data were very old or nonexistent. Such country-level data are important for citizens, clinicians, and policy makers so that local and global strategies to reduce the overall burden of stroke can be implemented. Through this first annual review of country-specific stroke epidemiology, we hope to promote discussion and provide insights into the worldwide burden of stroke.
|
International journal of stroke : official journal of the International Stroke Society
| 2,014
| 1
| 6
| 108
|
25,089,881
|
Post-error slowing is influenced by cognitive control demand.
|
Post-error slowing (PES) has been shown to reflect a control failure due to automatic attentional capture by the error. Here we aimed to assess whether PES also involves an increase in cognitive control. Using a cued-task-switching paradigm (Experiment 1) and a Stroop task (Experiment 2), the demand for top down control was manipulated. In Experiment 1, one group received dimension cues indicating the relevant stimulus dimension (e.g., "number") without specifying the response-category-to-key mapping, hence requiring considerable top down control. Another group was shown mapping cues providing information regarding both the relevant task identity and its category-to-key mapping (e.g., "one three"), requiring less top down control, and the last group received both types of cues, intermixed. In Experiment 2, one group performed a pure incongruent Stroop condition (name ink color of incongruent color names, high control demand), and another group received a pure neutral Stroop condition (name color patches, low control demand). In Experiment 2a, participants received the two conditions, intermixed. A larger PES was observed with dimension cues as compared with mapping cues, and with incongruent Stroop stimuli as compared to neutral stimuli, but not when the conditions were intermixed. These findings reveal that PES is influenced by the control demands that characterize the given block-wide experimental context and show that proactive cognitive control is involved in PES.
|
Acta psychologica
| 2,014
| 10
| 2
| 9
|
27,416,922
|
Anomalous vascularization in a Wnt medulloblastoma: a case report.
|
Medulloblastoma is the most common malignant brain tumor in children. To date only few cases of medulloblastoma with hemorrhages have been reported in the literature. Although some studies speculate on the pathogenesis of this anomalous increased vascularization in medulloblastoma, the specific mechanism is still far from clearly understood. A correlation between molecular medulloblastoma subgroups and hemorrhagic features has not been reported, although recent preliminary studies described that WNT-subtype tumors display increased vascularization and hemorrhaging.
|
BMC neurology
| 2,016
| 7
| 0
| 6
|
21,245,904
|
Epigenetic regulation of learning and memory by Drosophila EHMT/G9a.
|
The epigenetic modification of chromatin structure and its effect on complex neuronal processes like learning and memory is an emerging field in neuroscience. However, little is known about the "writers" of the neuronal epigenome and how they lay down the basis for proper cognition. Here, we have dissected the neuronal function of the Drosophila euchromatin histone methyltransferase (EHMT), a member of a conserved protein family that methylates histone 3 at lysine 9 (H3K9). EHMT is widely expressed in the nervous system and other tissues, yet EHMT mutant flies are viable. Neurodevelopmental and behavioral analyses identified EHMT as a regulator of peripheral dendrite development, larval locomotor behavior, non-associative learning, and courtship memory. The requirement for EHMT in memory was mapped to 7B-Gal4 positive cells, which are, in adult brains, predominantly mushroom body neurons. Moreover, memory was restored by EHMT re-expression during adulthood, indicating that cognitive defects are reversible in EHMT mutants. To uncover the underlying molecular mechanisms, we generated genome-wide H3K9 dimethylation profiles by ChIP-seq. Loss of H3K9 dimethylation in EHMT mutants occurs at 5% of the euchromatic genome and is enriched at the 5' and 3' ends of distinct classes of genes that control neuronal and behavioral processes that are corrupted in EHMT mutants. Our study identifies Drosophila EHMT as a key regulator of cognition that orchestrates an epigenetic program featuring classic learning and memory genes. Our findings are relevant to the pathophysiological mechanisms underlying Kleefstra Syndrome, a severe form of intellectual disability caused by mutations in human EHMT1, and have potential therapeutic implications. Our work thus provides novel insights into the epigenetic control of cognition in health and disease.
|
PLoS biology
| 2,011
| 1
| 7
| 62
|
19,707,552
|
An empirical explanation of the speed-distance effect.
|
Understanding motion perception continues to be the subject of much debate, a central challenge being to account for why the speeds and directions seen accord with neither the physical movements of objects nor their projected movements on the retina. Here we investigate the varied perceptions of speed that occur when stimuli moving across the retina traverse different projected distances (the speed-distance effect). By analyzing a database of moving objects projected onto an image plane we show that this phenomenology can be quantitatively accounted for by the frequency of occurrence of image speeds generated by perspective transformation. These results indicate that speed-distance effects are determined empirically from accumulated past experience with the relationship between image speeds and moving objects.
|
PloS one
| 2,009
| 8
| 0
| 3
|
30,677,250
|
Suicide risk in adolescents with fetal alcohol spectrum disorders.
|
The teratogenic effects of prenatal alcohol exposure (PAE) have been extensively documented over the course of 45 years of research and psychiatric problems are pervasive in this population. In adults with PAE, suicidal risk is high but less is known about the suicidal risk in adolescents with fetal alcohol spectrum disorders (FASD). This study describes the prevalence of suicidal ideation and serious suicide attempts in a sample of 54 adolescents between the ages of 13 and 18 years with FASD.
|
Birth defects research
| 2,019
| 7
| 2
| 28
|
28,299,788
|
Narratives of effort among Chinese, Hungarian and Chinese immigrant students in Hungary.
|
The present study aimed to reveal the effect of migration processes on the conceptualisation of effort involving two cultures with different approaches towards effort: China with an effort-promoting mindset and Hungary with an effort-repressing mindset. In the study, narrative approach was used in cross-sectional design involving Chinese, Hungarian and Chinese immigrant students living in Hungary. Altogether 139 students-49 Hungarian, 47 Chinese, 43 Chinese immigrants-aged 13-15 years provided narratives on past personal effort. Content analyses were done on 222 narratives. The results showed that the Chinese narratives of effort were characterised by learning and achievement orientation with elaborated effort process. In contrast, the Hungarian narratives were characterised by relationship orientation and emotional coping with a non-elaborated effort process. The narratives of the Chinese immigrants showed great similarity to those of the Chinese students reflecting academic effort, achievement goals and elaborated process. The findings suggest that the traditional Chinese approach towards effort persists in cultural transition, and academic effort tends to be a primary resource for educational success for the Chinese immigrant students in Hungary.
|
International journal of psychology : Journal international de psychologie
| 2,019
| 2
| 1
| 5
|
26,993,576
|
Kainate-induced network activity in the anterior cingulate cortex.
|
Anterior cingulate cortex (ACC) plays a pivotal role in higher order processing of cognition, attention and emotion. The network oscillation is considered an essential means for integration of these CNS functions. The oscillation power and coherence among related areas are often dis-regulated in several psychiatric and pathological conditions with a hemispheric asymmetric manner. Here we describe the network-based activity of field potentials recorded from the superficial layer of the mouse ACC in vitro using submerged type recordings. A short activation by kainic acid administration to the preparation induced populational activities ranging over several frequency bands including theta (3-8Hz), alpha (8-12Hz), beta (13-30Hz), low gamma (30-50Hz) and high gamma (50-80Hz). These responses were repeatable and totally abolished by tetrodotoxin, and greatly diminished by inhibitors of ionotropic and metabotropic glutamate receptors, GABAA receptor or gap-junctions. These observations suggest that the kainate-induced network activity can be a useful model of the network oscillation in the ACC circuit.
|
Neuroscience
| 2,016
| 6
| 0
| 5
|
29,335,424
|
Functionalisation of Detonation Nanodiamond for Monodispersed, Soluble DNA-Nanodiamond Conjugates Using Mixed Silane Bead-Assisted Sonication Disintegration.
|
Nanodiamonds have many attractive properties that make them suitable for a range of biological applications, but their practical use has been limited because nanodiamond conjugates tend to aggregate in solution during or after functionalisation. Here we demonstrate the production of DNA-detonation nanodiamond (DNA-DND) conjugates with high dispersion and solubility using an ultrasonic, mixed-silanization chemistry protocol based on the in situ Bead-Assisted Sonication Disintegration (BASD) silanization method. We use two silanes to achieve these properties: (1) 3-(trihydroxysilyl)propyl methylphosphonate (THPMP); a negatively charged silane that imparts high zeta potential and solubility in solution; and (2) (3-aminopropyl)triethoxysilane (APTES); a commonly used functional silane that contributes an amino group for subsequent bioconjugation. We target these amino groups for covalent conjugation to thiolated, single-stranded DNA oligomers using the heterobifunctional crosslinker sulfosuccinimidyl 4-(N-maleimidomethyl)cyclohexane-1-carboxylate (Sulfo-SMCC). The resulting DNA-DND conjugates are the smallest reported to date, as determined by Dynamic Light Scattering (DLS) and Atomic Force Microscopy (AFM). The functionalisation method we describe is versatile and can be used to produce a wide variety of soluble DND-biomolecule conjugates.
|
Scientific reports
| 2,018
| 1
| 1
| 17
|
20,519,541
|
Development of the selection and manipulation of self-generated thoughts in adolescence.
|
The ability to select and manipulate self-generated (stimulus-independent, SI), as opposed to stimulus-oriented (SO), information, in a controlled and flexible way has previously only been studied in adults. This ability is thought to rely in part on the rostrolateral prefrontal cortex (RLPFC), which continues to mature anatomically during adolescence. We investigated (1) the development of this ability behaviorally, (2) the associated functional brain development, and (3) the link between functional and structural maturation. Participants classified according to their shape letters either presented visually (SO phases) or that they generated in their head by continuing the alphabet sequence (SI phases). SI phases were performed in the presence or absence of distracting letters. A total of 179 participants (7-27 years old) took part in a behavioral study. Resistance to visual distractors exhibited small improvements with age. SI thoughts manipulation and switching between SI and SO thoughts showed steeper performance improvements extending into late adolescence. Thirty-seven participants (11-30 years old) took part in a functional MRI (fMRI) study. SI thought manipulation and switching between SO and SI thought were each associated with brain regions consistently recruited across age. A single frontal brain region in each contrast exhibited decreased activity with age: left inferior frontal gyrus/anterior insula for SI thought manipulation, and right superior RLPFC for switching between SO and SI thoughts. By integrating structural and functional data, we demonstrated that the observed functional changes with age were not purely consequences of structural maturation and thus may reflect the maturation of neurocognitive strategies.
|
The Journal of neuroscience : the official journal of the Society for Neuroscience
| 2,010
| 6
| 3
| 22
|
33,681,590
|
Altered Cholesterol Biosynthesis Affects Drug Metabolism.
|
The last step of cholesterol biosynthesis is the conversion of 7-dehydrocholesterol (7-DHC) into cholesterol, a reaction catalyzed by dehydrocholesterol reductase 7 (DHCR7). Investigation of the effect of
|
ACS omega
| 2,021
| 3
| 0
| 1
|
30,643,290
|
Cannabinoid CB
|
Major depressive disorder is a devastating psychiatric disease that afflicts up to 17% of the world's population. Postmortem brain analyses and imaging studies of patients with depression have implicated basal lateral amygdala (BLA) dysfunction in the pathophysiology of depression. However, the circuit and molecular mechanisms through which BLA neurons modulate depressive behavior are largely uncharacterized. Here, in mice, we identified that BLA cholecystokinin (CCK) glutamatergic neurons mediated negative reinforcement via D2 medium spiny neurons (MSNs) in the nucleus accumbens (NAc) and that chronic social defeat selectively potentiated excitatory transmission of the CCK
|
Nature medicine
| 2,019
| 2
| 10
| 130
|
32,931,106
|
Perinatal mental health: a review of progress and challenges.
|
Perinatal mental health has become a significant focus of interest in recent years, with investment in new specialist mental health services in some high-income countries, and inpatient psychiatric mother and baby units in diverse settings. In this paper, we summarize and critically examine the epidemiology and impact of perinatal mental disorders, including emerging evidence of an increase of their prevalence in young pregnant women. Perinatal mental disorders are among the commonest morbidities of pregnancy, and make an important contribution to maternal mortality, as well as to adverse neonatal, infant and child outcomes. We then review the current evidence base on interventions, including individual level and public health ones, as well as service delivery models. Randomized controlled trials provide evidence on the effectiveness of psychological and psychosocial interventions at the individual level, though it is not yet clear which women with perinatal mental disorders also need additional support for parenting. The evidence base on psychotropic use in pregnancy is almost exclusively observational. There is little research on the full range of perinatal mental disorders, on how to improve access to treatment for women with psychosocial difficulties, and on the effectiveness of different service delivery models. We conclude with research and clinical implications, which, we argue, highlight the need for an extension of generic psychiatric services to include preconception care, and further investment into public health interventions, in addition to perinatal mental health services, potentially for women and men, to reduce maternal and child morbidity and mortality.
|
World psychiatry : official journal of the World Psychiatric Association (WPA)
| 2,020
| 10
| 30
| 502
|
23,723,544
|
Family history correlates of digit ratio abnormalities in schizophrenia.
|
The differences in digit ratio are proposed to arise due to differential effects of sex steroids on the growth of finger bones. In this study, we sought to examine the sex differences and the influence of family history of psychosis on digit ratio in patients with schizophrenia compared to matched healthy controls (HCs).
|
Indian journal of psychological medicine
| 2,012
| 10
| 0
| 2
|
32,414,579
|
High on-clopidogrel platelet reactivity in ischaemic stroke or transient ischaemic attack: Systematic review and meta-analysis.
|
To assess the prevalence of high on-clopidogrel platelet reactivity (HCPR) in patients with ischaemic stroke or transient ischaemic attack (IS/TIA), their outcome and genetic basis of on-treatment response variability in IS/TIA patients.
|
Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association
| 2,020
| 7
| 2
| 26
|
33,380,468
|
Neural Encoding and Representation of Time for Sensorimotor Control and Learning.
|
The ability to perceive and produce movements in the real world with precise timing is critical for survival in animals, including humans. However, research on sensorimotor timing has rarely considered the tight interrelation between perception, action, and cognition. In this review, we present new evidence from behavioral, computational, and neural studies in humans and nonhuman primates, suggesting a pivotal link between sensorimotor control and temporal processing, as well as describing new theoretical frameworks regarding timing in perception and action. We first discuss the link between movement coordination and interval-based timing by addressing how motor training develops accurate spatiotemporal patterns in behavior and influences the perception of temporal intervals. We then discuss how motor expertise results from establishing task-relevant neural manifolds in sensorimotor cortical areas and how the geometry and dynamics of these manifolds help reduce timing variability. We also highlight how neural dynamics in sensorimotor areas are involved in beat-based timing. These lines of research aim to extend our understanding of how timing arises from and contributes to perceptual-motor behaviors in complex environments to seamlessly interact with other cognitive processes.
|
The Journal of neuroscience : the official journal of the Society for Neuroscience
| 2,021
| 2
| 7
| 41
|
27,105,112
|
Methylome-wide Analysis of Chronic HIV Infection Reveals Five-Year Increase in Biological Age and Epigenetic Targeting of HLA.
|
HIV-infected individuals are living longer on antiretroviral therapy, but many patients display signs that in some ways resemble premature aging. To investigate and quantify the impact of chronic HIV infection on aging, we report a global analysis of the whole-blood DNA methylomes of 137 HIV+ individuals under sustained therapy along with 44 matched HIV- individuals. First, we develop and validate epigenetic models of aging that are independent of blood cell composition. Using these models, we find that both chronic and recent HIV infection lead to an average aging advancement of 4.9 years, increasing expected mortality risk by 19%. In addition, sustained infection results in global deregulation of the methylome across >80,000 CpGs and specific hypomethylation of the region encoding the human leukocyte antigen locus (HLA). We find that decreased HLA methylation is predictive of lower CD4 / CD8 T cell ratio, linking molecular aging, epigenetic regulation, and disease progression.
|
Molecular cell
| 2,016
| 4
| 13
| 134
|
18,539,159
|
Application of positron emission tomography to neuroimaging in sports sciences.
|
To investigate exercise-induced regional metabolic and perfusion changes in the human brain, various methods are available, such as positron emission tomography (PET), functional magnetic resonance imaging (fMRI), near-infrared spectroscopy (NIRS) and electroencephalography (EEG). In this paper, details of methods of metabolic measurement using PET, [(18)F]fluorodeoxyglucose ([(18)F]FDG) and [(15)O]radio-labelled water ([(15)O]H(2)O) will be explained. Functional neuroimaging in the field of neuroscience was started in the 1970s using an autoradiography technique on experimental animals. The first human functional neuroimaging exercise study was conducted in 1987 using a rough measurement system known as (133)Xe inhalation. Although the data was useful, more detailed and exact functional neuroimaging, especially with respect to spatial resolution, was achieved by positron emission tomography. Early studies measured the cerebral blood flow changes during exercise. Recently, PET was made more applicable to exercise physiology and psychology by the use of the tracer [(18)F]FDG. This technique allowed subjects to be scanned after an exercise task is completed but still obtain data from the exercise itself, which is similar to autoradiography studies. In this report, methodological information is provided with respect to the recommended protocol design, the selection of the scanning mode, how to evaluate the cerebral glucose metabolism and how to interpret the regional brain activity using voxel-by-voxel analysis and regions of interest techniques (ROI). Considering the important role of exercise in health promotion, further efforts in this line of research should be encouraged in order to better understand health behavior. Although the number of research papers is still limited, recent work has indicated that the [(18)F]FDG-PET technique is a useful tool to understand brain activity during exercise.
|
Methods (San Diego, Calif.)
| 2,008
| 8
| 2
| 17
|
26,348,559
|
Imaging fast electrical activity in the brain with electrical impedance tomography.
|
Imaging of neuronal depolarization in the brain is a major goal in neuroscience, but no technique currently exists that could image neural activity over milliseconds throughout the whole brain. Electrical impedance tomography (EIT) is an emerging medical imaging technique which can produce tomographic images of impedance changes with non-invasive surface electrodes. We report EIT imaging of impedance changes in rat somatosensory cerebral cortex with a resolution of 2ms and <200μm during evoked potentials using epicortical arrays with 30 electrodes. Images were validated with local field potential recordings and current source-sink density analysis. Our results demonstrate that EIT can image neural activity in a volume 7×5×2mm in somatosensory cerebral cortex with reduced invasiveness, greater resolution and imaging volume than other methods. Modeling indicates similar resolutions are feasible throughout the entire brain so this technique, uniquely, has the potential to image functional connectivity of cortical and subcortical structures.
|
NeuroImage
| 2,016
| 1
| 6
| 75
|
21,769,566
|
Tryptophan depletion disinhibits punishment but not reward prediction: implications for resilience.
|
We have previously shown that tryptophan depletion enhances punishment but not reward prediction (Cools et al. in Neuropsychopharmacology 33:2291-2299, 2008b). This provided evidence for a valence-specific role of serotonin (which declines under depleted tryptophan) in aversive processing. Recent theoretical (Dayan and Huys in PLoS Comput Biol 4:e4, 2008) and experimental (Crockett et al. in J Neurosci 29:11993-11999, 2009) approaches have, however, further specified this role by showing that serotonin is critical for punishment-induced inhibition.
|
Psychopharmacology
| 2,012
| 1
| 6
| 36
|
22,686,849
|
It's all in the detail: intentional forgetting of autobiographical memories using the autobiographical think/no-think task.
|
Using a novel autobiographical think/no-think procedure (ATNT; a modified version of the think/no-think task), 2 studies explored the extent to which we possess executive control over autobiographical memory. In Study 1, 30 never-depressed participants generated 12 positive and 12 negative autobiographical memories. Memories associated with cue-personal word pairings were learned to criterion. Participants were then asked to recall the memory associated with some of the cue-personal word pairs (i.e., think condition) or to avoid saying or thinking about the memory associated with others (i.e., no-think condition). In a subsequent test of recall, systematic forgetting effects emerged for no-think autobiographical memories compared to baseline that received neither no-think nor think instructions. These findings were extended and replicated in a second ATNT study (using a further 30 never-depressed participants), which showed that the forgetting of autobiographical memories in the no-think condition was unlikely to be a function of thought substitution or demand characteristics.
|
Journal of experimental psychology. Learning, memory, and cognition
| 2,013
| 3
| 5
| 27
|
29,448,961
|
Nuclear receptor agonist-driven modification of inflammation and amyloid pathology enhances and sustains cognitive improvements in a mouse model of Alzheimer's disease.
|
Alzheimer's disease (AD) is a highly prevalent neurodegenerative disorder characterized by pathological hallmarks of beta-amyloid plaque deposits, tau pathology, inflammation, and cognitive decline. Treatment remains a clinical obstacle due to lack of effective therapeutics. Agonists targeting nuclear receptors, such as bexarotene, reversed cognitive deficits regardless of treatment duration and age in murine models of AD. While bexarotene demonstrated marked efficacy in decreasing plaque levels following short-term treatment, prolonged treatment did not modulate plaque burden. This suggested that plaques might reform in mice treated chronically with bexarotene and that cessation of bexarotene treatment before plaques reform might alter amyloid pathology, inflammation, and cognition in AD mice.
|
Journal of neuroinflammation
| 2,018
| 2
| 1
| 15
|
33,554,561
|
The anti-inflammatory cytokine response characterized by elevated interleukin-10 is a stronger predictor of severe disease and poor outcomes than the pro-inflammatory cytokine response in coronavirus disease 2019 (COVID-19).
|
Severe coronavirus disease 2019 (COVID-19) is associated with a dysregulated immune state. While research has focused on the hyperinflammation, little research has been performed on the compensatory anti-inflammatory response. The aim of this study was to evaluate the anti-inflammatory cytokine response to COVID-19, by assessing interleukin-10 (IL-10) and IL-10/lymphocyte count ratio and their association with outcomes.
|
Clinical chemistry and laboratory medicine
| 2,021
| 2
| 12
| 31
|
18,824,069
|
Effects of salvinorin A on locomotor sensitization to D2/D3 dopamine agonist quinpirole.
|
Locomotor sensitization induced by the dopamine agonist quinpirole can be potentiated by co-treatment with the synthetic kappa opioid agonist U69593. The identification of salvinorin A, an active component of the psychotropic sage Salvia divinorum, as a structurally different agonist of kappa-opioid receptors raised the question of whether this compound would similarly potentiate sensitization to quinpirole. Rats were co-treated with 0.5 mg/kg quinpirole and either salvinorin A (0.04, 0.4 or 2.0 mg/kg) or U69593 (0.3 mg/kg). Control groups were co-treated with vehicle and saline, vehicle and quinpirole (0.5 mg/kg), or saline and salvinorin A (0.4 mg/kg). Rats were injected biweekly for a total of 10 injections and locomotor activity measured after each treatment. Results showed that the highest dose of salvinorin A potentiated sensitization to quinpirole as did U69593, the middle salvinorin A dose had no effect on quinpirole sensitization, and the lowest dose of salvinorin A attenuated sensitization to quinpirole. These findings indicate that structural differences between salvinorin A and U69593 do not affect the potentiation of quinpirole sensitization. Moreover, the opposite effects of high and low salvinorin A doses suggest that salvinorin A can produce bidirectional modulation of sensitization to dopamine agonists.
|
Neuroscience letters
| 2,008
| 12
| 1
| 7
|
18,644,337
|
Social learning: nectar robbing spreads socially in bumble bees.
|
Social transmission of learned behaviour is well documented in vertebrates but much less so among invertebrates. New research shows that nectar robbing can spread socially among bumble bees, even in the absence of nectar-robbing models.
|
Current biology : CB
| 2,008
| 7
| 0
| 2
|
26,382,105
|
Structural brain network analysis in families multiply affected with bipolar I disorder.
|
Disrupted structural connectivity is associated with psychiatric illnesses including bipolar disorder (BP). Here we use structural brain network analysis to investigate connectivity abnormalities in multiply affected BP type I families, to assess the utility of dysconnectivity as a biomarker and its endophenotypic potential. Magnetic resonance diffusion images for 19 BP type I patients in remission, 21 of their first degree unaffected relatives, and 18 unrelated healthy controls underwent tractography. With the automated anatomical labelling atlas being used to define nodes, a connectivity matrix was generated for each subject. Network metrics were extracted with the Brain Connectivity Toolbox and then analysed for group differences, accounting for potential confounding effects of age, gender and familial association. Whole brain analysis revealed no differences between groups. Analysis of specific mainly frontal regions, previously implicated as potentially endophenotypic by functional magnetic resonance imaging analysis of the same cohort, revealed a significant effect of group in the right medial superior frontal gyrus and left middle frontal gyrus driven by reduced organisation in patients compared with controls. The organisation of whole brain networks of those affected with BP I does not differ from their unaffected relatives or healthy controls. In discreet frontal regions, however, anatomical connectivity is disrupted in patients but not in their unaffected relatives.
|
Psychiatry research
| 2,015
| 10
| 0
| 16
|
22,869,990
|
Yoga therapy for Schizophrenia.
|
Schizophrenia is one of the most severe mental disorders. Despite significant advances in pharmacotherapy, treatment remains sub-optimal, with many patients having persisting deficits, especially in cognitive and social functioning. Yoga as a therapy has proven to be effective as a sole or additional intervention in psychiatric disorders such as depression and anxiety. Recently, there has been significant interest in the application of yoga therapy in psychosis and schizophrenia. To review a) the evidence for the use of yoga therapy in patients with schizophrenia b) studies which have been done in this area, c) the barriers for reaching yoga to patients, and d) future directions, an English language literature search of PubMed/MEDLINE, Google Scholar, and EBSCO as well as grey literature was done. Research reports have demonstrated the feasibility and efficacy of yoga as an add-on therapy in schizophrenia, particularly in improving negative symptomatology and social cognition. However, the biological underpinnings of this effect remain unclear, although there are some indications that hormones like oxytocin may contribute to the changes in social cognition.
|
International journal of yoga
| 2,012
| 7
| 6
| 22
|
19,072,513
|
Premenopausal oophorectomy and the risk for dementia.
|
Evaluation of: Rocca WA, Bower JH, Maraganore DM et al.: Increased risk of cognitive impairment or dementia in women who underwent oophorectomy before menopause. Neurology 69(11), 1074-1083 (2007). This study examines the incidence of dementia in a population of women who underwent unilateral or bilateral oophorectomy before menopause. Patients were drawn from the Mayo Clinic database and included women who had surgical removal of either one or both ovaries during a preceding 40-year period (1950-1987), as well as a reference group of women who did not undergo oophorectomy. Women who agreed to participate in the study were interviewed by phone and received a modified Telephone Interview for Cognition or a brief dementia questionnaire answered by a proxy if the subject was deceased or incapacitated. Women who had unilateral oophorectomy had a greater incidence of dementia as compared with surgical controls. In women with bilateral oophorectomies, the risk for dementia was increased in women who were younger at the time of surgery as well as in women who discontinued estrogen therapy before 50 years of age.
|
Women's health (London, England)
| 2,008
| 3
| 0
| 3
|
30,982,599
|
Primate Amygdala Neurons Simulate Decision Processes of Social Partners.
|
By observing their social partners, primates learn about reward values of objects. Here, we show that monkeys' amygdala neurons derive object values from observation and use these values to simulate a partner monkey's decision process. While monkeys alternated making reward-based choices, amygdala neurons encoded object-specific values learned from observation. Dynamic activities converted these values to representations of the recorded monkey's own choices. Surprisingly, the same activity patterns unfolded spontaneously before partner's choices in separate neurons, as if these neurons simulated the partner's decision-making. These "simulation neurons" encoded signatures of mutual-inhibitory decision computation, including value comparisons and value-to-choice conversions, resulting in accurate predictions of partner's choices. Population decoding identified differential contributions of amygdala subnuclei. Biophysical modeling of amygdala circuits showed that simulation neurons emerge naturally from convergence between object-value neurons and self-other neurons. By simulating decision computations during observation, these neurons could allow primates to reconstruct their social partners' mental states.
|
Cell
| 2,019
| 5
| 11
| 56
|
18,279,887
|
Validated sandwich ELISA for the quantification of tissue transglutaminase in tissue homogenates and cell lysates of multiple species.
|
Tissue transglutaminase (tTG) is a calcium dependent enzyme that displays diverse functions in various physiological processes. In addition to these physiological functions, there is strong evidence for the implication of tTG in a number of pathologies, including celiac disease, cancer and neurodegeneration. To explore the expression and function of tTG during (patho)physiological conditions, it is of utmost importance to have an assay that specifically measures tTG protein levels in various species and matrices. Therefore, we have developed a sensitive sandwich ELISA to measure tTG protein levels in tissue homogenates and cell lysates of human, rat and mouse origin. The ELISA uses commercially available antibodies, and human recombinant tTG as the standard protein. The limit of detection is 100 pg/ml; the coefficients of intra- and inter-assay variation range from 2.4% to 6.6% and from 12.7% to 15.1%, respectively. Clear detectable levels of tTG protein were measured in human and rat liver and cerebral cortex, as well as in brain-derived neuronal and glial cells. tTG levels in mouse tissues were much lower than observed in human and rat tissues. No cross-reactivity against keratinocyte TG (TG1), epidermal TG (TG3) or blood coagulation factor XIII was observed. The tTG specific sandwich ELISA presented in this paper is a sensitive and reliable tool to accurately measure tTG protein levels in different matrices (cell/tissue) of rat, mouse and human origin. It provides a better alternative for the widely used transglutaminase activity assay with respect to sensitivity and specificity, and may serve as a valuable tool to investigate protein expression levels as part of the approach to unravel the contribution of tTG to health and disease.
|
Journal of immunological methods
| 2,008
| 3
| 0
| 7
|
31,955,980
|
Mutations in the J domain of DNAJB6 cause dominant distal myopathy.
|
Eight patients from five families with undiagnosed dominant distal myopathy underwent clinical, neurophysiological and muscle biopsy examinations. Molecular genetic studies were performed using targeted sequencing of all known myopathy genes followed by segregation of the identified mutations in the affected families using Sanger sequencing. Two novel mutations in DNAJB6 J domain, c.149C>T (p.A50V) and c.161A>C (p.E54A), were identified as the cause of disease. The muscle involvement with p.A50V was distal calf-predominant, and the p.E54A was more proximo-distal. Histological findings were similar to those previously reported in DNAJB6 myopathy. In line with reported pathogenic mutations in the glycine/phenylalanine (G/F) domain of DNAJB6, both the novel mutations showed reduced anti-aggregation capacity by filter trap assay and TDP-43 disaggregation assays. Modeling of the protein showed close proximity of the mutated residues with the G/F domain. Myopathy-causing mutations in DNAJB6 are not only located in the G/F domain, but also in the J domain. The identified mutations in the J domain cause dominant distal and proximo-distal myopathy, confirming that mutations in DNAJB6 should be considered in distal myopathy cases.
|
Neuromuscular disorders : NMD
| 2,020
| 1
| 6
| 22
|
26,208,597
|
Geldanamycin Reduces Aβ-Associated Anxiety and Depression, Concurrent with Autophagy Provocation.
|
Neurodegenerative disorders are generally characterized by abnormal aggregation and deposition of specific proteins. Amyloid beta (Aβ)-associated neurodegenerative disorder is characterized by an oxidative damage that, in turn, leads to some behavioral changes before the establishment of dementia such as depression and anxiety. In the current study, we investigated the effect of heat shock protein 90 inhibitor geldanamycin (GA) administration 24 h before Aβ injection. In our experiment, 7 days after Aβ injection, elevated plus maze and forced swimming test were conducted to assess anxiety and depression-like behaviors. Levels of autophagy markers and malondialdehyde (MDA) and also activity of catalase in the hippocampus of rats were evaluated. Our behavioral analyses demonstrated that GA pretreatment can significantly decrease anxiety- and depression-like behaviors in Aβ-injected rats. Also, levels of autophagy markers including Atg12, Atg7, and LC3-II increased, while MDA level decreased and the activity of catalase increased in rats pretreated with GA compared to Aβ-injected rats. Thus, we assumed that GA, at least in part, ameliorated Aβ-mediated anxiety and depression by inducing autophagy and improving antioxidant defense system.
|
Journal of molecular neuroscience : MN
| 2,015
| 11
| 4
| 17
|
18,977,306
|
BDNF-induced synaptic delivery of AMPAR subunits is differentially dependent on NMDA receptors and requires ERK.
|
Previous studies using an in vitro model of eyeblink classical conditioning in turtles suggest that increased numbers of synaptic AMPARs supports the acquisition and expression of conditioned responses (CRs). Brain-derived neurotrophic factor (BDNF) and its associated receptor tyrosine kinase, TrkB, is also required for acquisition of CRs. Bath application of BDNF alone induces synaptic delivery of GluR1- and GluR4-containing AMPARs that is blocked by coapplication of the receptor tyrosine kinase inhibitor K252a. The molecular mechanisms involved in BDNF-induced AMPAR trafficking remain largely unknown. The aim of this study was to determine whether BDNF-induced synaptic AMPAR incorporation utilizes similar cellular mechanisms as AMPAR trafficking that occurs during in vitro classical conditioning. Using pharmacological blockade and confocal imaging, the results show that synaptic delivery of GluR1 subunits during conditioning or BDNF application does not require activity of NMDARs but is mediated by extracellular signal-regulated kinase (ERK). In contrast, synaptic delivery of GluR4-containing AMPARs during both conditioning and BDNF application is NMDAR- as well as ERK-dependent. These findings indicate that BDNF application mimics AMPAR trafficking observed during conditioning by activation of some of the same intracellular signaling pathways and suggest that BDNF is a key signal transduction element in postsynaptic events that mediate conditioning.
|
Neurobiology of learning and memory
| 2,009
| 3
| 4
| 29
|
28,609,587
|
Chemogenetic Modulation of G Protein-Coupled Receptor Signalling in Visual Attention Research.
|
Attention is a fundamental cognitive process involved in nearly all aspects of life. Abnormal attentional control is a symptom of many neurological disorders, most notably recognized in ADHD (attention deficit hyperactivity disorder). Although attentional performance and its malfunction has been a major area of investigation, it has proven difficult to accurately associate specific neuronal projections, cell types, neurotransmitter systems and receptors with distinct phenotypes owing to its complexity. In this MiniReview, we present a recently invented technology known as Designer Receptors Exclusively Activated by Designer Drugs (DREADDs). The DREADD technology is an emerging and transformative method that allows selective manipulation of G protein-coupled receptor (GPCR) signalling, and its broad-ranging usefulness in attention research is now beginning to emerge. We first describe the different DREADDs available and explain how unprecedented specificity of neuronal signalling can be achieved using DREADDs. We next discuss various studies performed in animal models of visual attention, where different brain regions and neuronal populations have been probed by DREADDs. We highlight the interplay between the dopamine (DA) and noradrenaline (NA) catecholamine systems in visual attention and explain why DREADD technology can untangle and help us better understand such complex systems in normal and malfunctioning conditions.
|
Basic & clinical pharmacology & toxicology
| 2,017
| 11
| 1
| 4
|
27,072,014
|
Brain Activation Patterns Characterizing Different Phases of Motor Action: Execution, Choice and Ideation.
|
Motor behaviour is controlled by a large set of interacting neural structures, subserving the different components involved in hierarchical motor processes. Few studies have investigated the neural substrate of higher-order motor ideation, i.e. the mental operation of conceiving a movement. The aim of this functional magnetic resonance imaging study was to segregate the neural structures involved in motor ideation from those involved in movement choice and execution. An index finger movement paradigm was adopted, including three different conditions: performing a pre-specified movement, choosing and executing a movement and ideating a movement of choice. The tasks involved either the right or left hand, in separate runs. Neuroimaging results were obtained by comparing the different experimental conditions and computing conjunction maps of the right and left hands for each contrast. Pre-specified movement execution was supported by bilateral fronto-parietal motor regions, the cerebellum and putamen. Choosing and executing finger movement involved mainly left fronto-temporal areas and the anterior cingulate. Motor ideation activated almost exclusively left hemisphere regions, including the inferior, middle and superior frontal regions, middle temporal and middle occipital gyri. These findings show that motor ideation is controlled by a cortical network mainly involved in abstract thinking, cognitive and motor control, semantic and visual imagery processes.
|
Brain topography
| 2,016
| 9
| 0
| 7
|
21,295,077
|
Social encounter with a novel partner in adolescent rats: activation of the central endocannabinoid system.
|
The endocannabinoid system is critically involved in the modulation of affect, motivation, and emotion. Here, we investigated the hypothesis that changes in the content of endocannabinoid levels might underlie adaptation to positive social conditions during adolescence. To this aim, separate pairs of adolescent (postnatal days 32-35) male Wistar rats were allowed to interact in a neutral cage under two different testing conditions, i.e. familiar (FAM) and non-familiar (NFAM) social partners. We found that adolescent rats that encountered a NFAM partner spent significantly more time Sniffing and Following the companion than subjects exposed to a FAM partner, whereas no changes in levels of rough-and-tumble play were observed. Notably, the NFAM social encounter significantly increased striatal anandamide (AEA) levels compared to both non-social controls and animals that encountered a FAM partner. Changes in AEA levels appeared to be region-specific, since no changes were observed in the other brain regions analysed, neither were they observed in the activity of the AEA-hydrolase (FAAH) nor in the content of the other major endocannabinoid 2-arachidonylglycerol. In addition, animals that encountered a NFAM partner tended to explore less extensively the illuminated compartment of the light-dark box when compared to animals that had previously encountered a FAM companion. In conclusion, striatal AEA levels seem to participate in the emotional arousal resulting from a NFAM social encounter in adolescent rats, and to be particularly important for coping response to novel social contexts.
|
Behavioural brain research
| 2,011
| 6
| 1
| 12
|
32,745,958
|
Trait impulsivity correlates with active myoclonic seizures in genetic generalized epilepsy.
|
Juvenile myoclonic epilepsy (JME) is a common subtype of genetic generalized epilepsy (GGE) arising in adolescence and is often associated with executive function (EF) deficits. Some EF components like response inhibition have been extensively evaluated in JME, but few studies have focused upon trait impulsivity or compared between GGE subtypes. The aim of the present study was to compare the association of trait impulsivity in JME with other GGE subtypes.
|
Epilepsy & behavior : E&B
| 2,020
| 11
| 1
| 11
|
26,176,805
|
A Randomized Prospective Double-Blind Comparison Trial of Clomiphene Citrate and Anastrozole in Raising Testosterone in Hypogonadal Infertile Men.
|
Clomiphene citrate (CC) and anastrozole (AZ) have been used off label to increase testosterone (T) in hypogonadal infertile men (HIM). Both medications have been shown to increase T with different effects on estradiol (E2) and T-to-E2 ratios. There are no reported randomized trials comparing CC and AZ to improve T levels in HIM. We aimed to establish equivalence of CC vs. AZ with respect to improvement in T levels in HIM.
|
The journal of sexual medicine
| 2,015
| 8
| 6
| 37
|
21,452,238
|
Surface-associated astrocytes, not endfeet, form the glia limitans in posterior piriform cortex and have a spatially distributed, not a domain, organization.
|
"Surface-associated astrocytes" (SAAs) in posterior piriform cortex (PPC) are unique by virtue of a direct apposition to the cortical surface and large-caliber processes that descend into layer I. In this study additional unique and functionally relevant features of SAAs in PPC of the rat were identified by light and electron microscopy. Examination of sections cut parallel to the surface of PPC and stained for glial fibrillar acidic protein revealed that, in addition to descending processes, SAAs give rise to an extensive matrix of "superficial processes." Electron microscopy revealed that these superficial processes, together with cell bodies, form a continuous sheet at the surface of PPC with features in common with the glia limitans that is formed by endfeet in other cortical areas. These include a glia limiting membrane with basal lamina and similar associated organelles, including a striking array of mitochondria. Of particular interest, SAAs lack the domain organization observed in neocortex and hippocampus. Rather, superficial processes overlap extensively with gap junctions between their proximal regions as well as between cell bodies. Study of the descending processes revealed thin extensions, many of which appose synaptic profiles. We conclude that SAAs provide a potential substrate for bidirectional signaling and transport between brain and the pial arteries and cerebrospinal fluid in the subarachnoid space. We postulate that the spatially distributed character of SAAs in PPC reflects and supports the spatially distributed circuitry and sensory representation that are also unique features of this area.
|
The Journal of comparative neurology
| 2,011
| 7
| 0
| 6
|
25,475,988
|
Posterior compensatory network in cognitively intact elders with hippocampal atrophy.
|
Functional compensation in late life is poorly understood but may be vital to understanding long-term cognitive trajectories. To study this we first established an empirically derived threshold to distinguish hippocampal atrophy in those with Mild Cognitive Impairment (MCI n = 34) from those with proficient cognition (PRO n = 22), using data from a population-based cohort. Next, to identify compensatory networks we compared cortical activity patterns during a graded spatial working memory (SWM) task in only cognitively proficient individuals, either with (PROATR ) or without hippocampal atrophy (PRONIL ). Multivariate Partial Least Squares analyses revealed that these groups engaged spatially distinct SWM-related networks. In those with hippocampal atrophy and under conditions of basic-SWM demand, expression of a posterior compensatory network (PCN) comprised calcarine and posterior parietal cortex strongly correlated with superior SWM performance (r = -0.96). In these individuals, basic level SWM response times were faster and no less accurate than in those with no hippocampal atrophy. Cognitively proficient older individuals with hippocampal atrophy may, therefore, uniquely engage posterior brain areas when performing simple spatial working memory tasks.
|
Hippocampus
| 2,015
| 5
| 0
| 3
|
34,134,697
|
Fruit bats adjust their foraging strategies to urban environments to diversify their diet.
|
Urbanization is one of the most influential processes on our globe, putting a great number of species under threat. Some species learn to cope with urbanization, and a few even benefit from it, but we are only starting to understand how they do so. In this study, we GPS tracked Egyptian fruit bats from urban and rural populations to compare their movement and foraging in urban and rural environments. Because fruit trees are distributed differently in these two environments, with a higher diversity in urban environments, we hypothesized that foraging strategies will differ too.
|
BMC biology
| 2,021
| 6
| 2
| 22
|
23,827,140
|
[Sexual dysfunction and depression: Validity of a French version of the ASEX scale].
|
Since the Beck study (1967), it is well known that sexual dysfunction is particularly prevalent in depressive patients compared to the general population, at 70% and 30% respectively. Depression, psychotropics and antidepressants are responsible for altering sexuality, and patients are considerably affected by these symptoms that dramatically decrease their quality of life. Screening for sexual dysfunctions seems essential, and a scale such as the Arizona Sexual Experience Scale (ASEX) may help practitioners. The English version of this scale was validated in 2000 (McGahuey et al. [9]), and is widely used in scientific research. The aim of this study was to assess the validity of the French version of the ASEX scale.
|
L'Encephale
| 2,014
| 4
| 3
| 5
|
29,368,253
|
The interface between child/adolescent and adult mental health services: results from a European 28-country survey.
|
Transition-related discontinuity of care is a major socioeconomic and societal challenge for the EU. The current service configuration, with distinct Child and Adolescent Mental Health (CAMHS) and Adult Mental Health Services (AMHS), is considered a weak link where the care pathway needs to be most robust. Our aim was to delineate transitional policies and care across Europe and to highlight current gaps in care provision at the service interface. An online mapping survey was conducted across all 28 European Countries using a bespoke instrument: The Standardized Assessment Tool for Mental Health Transition (SATMEHT). The survey was directed at expert(s) in each of the 28 EU countries. The response rate was 100%. Country experts commonly (12/28) reported that between 25 and 49% of CAMHS service users will need transitioning to AMHS. Estimates of the percentage of AMHS users aged under 30 years who had has previous contact with CAMHS were most commonly in the region 20-30% (33% on average).Written policies for managing the interface were available in only four countries and half (14/28) indicated that no transition support services were available. This is the first survey of CAMHS transitional policies and care carried out at a European level. Policymaking on transitional care clearly needs special attention and further elaboration. The Milestone Study on transition should provide much needed data on transition processes and outcomes that could form the basis for improving policy and practice in transitional care.
|
European child & adolescent psychiatry
| 2,018
| 4
| 6
| 66
|
28,395,802
|
Reprogramming of a human induced pluripotent stem cell (iPSC) line from a Parkinson's disease patient with a R1628P variant in the LRRK2 gene.
|
Peripheral blood mononuclear cells (PBMCs) were collected from a clinically diagnosed 59-year old male Parkinson's disease (PD) patient with R1628P variant in the LRRK2 gene. The PMBCs were reprogrammed with the human OSKM transcription factors using the Sendai-virus reprogramming system. The transgene-free iPSC showed pluripotency confirmed by immunofluorescent staining for pluripotency markers and differentiated into the 3 germ layers in vivo. The iPSC line also showed normal karyotype. This cellular model will provide a good resource for further pathophysiological studies of PD.
|
Stem cell research
| 2,017
| 1
| 0
| 7
|
19,409,199
|
An Ang1-Tie2-PI3K axis in neural progenitor cells initiates survival responses against oxygen and glucose deprivation.
|
Neural progenitor cells (NPCs) have the potential to survive brain ischemia and participate in neurogenesis after stroke. However, it is not clear how survival responses are initiated in NPCs. Using embryonic mouse NPCs and the in vitro oxygen and glucose deprivation (OGD) model, we found that angiopoietin-1 (Ang1) could prevent NPCs from OGD-induced apoptosis, as evidenced by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling and annexin V labeling. Ang1 significantly elevated tunica intima endothelial kinase 2 (Tie2) autophosphorylation level, suggesting the existence of functional Tie2 receptors on NPCs. NPCs under OGD conditions exhibited reduction of Akt phosphorylation, decrease of the Bcl-2/Bax ratio, activation of caspase-3, cleavage of PARP, and downregulation of beta-catenin and nestin. Ang1 reversed the above changes concomitantly with significant rising of survival rates of NPCs under OGD, but all these effects of Ang1 could be blocked by either soluble extracellular domain of Tie2 Fc fusion protein (sTie2Fc) or the phosphoinositide 3-kinase (PI3K) inhibitor 2-(4-morpholinyl)-8-phenyl-1(4H)-benzopyran-4-one (LY294002). Our findings suggest the existence of an Ang1-Tie2-PI3K signaling axis that is essential in initiation of survival responses in NPCs against cerebral ischemia and hypoxia.
|
Neuroscience
| 2,009
| 5
| 2
| 15
|
33,098,221
|
Delusional infestation: Clinical presentations, diagnosis, and management.
|
Delusional infestation is a primary psychiatric disorder characterized by a somatic-type delusional disorder (primary delusional infestation) that may lead to self-induced cutaneous lesions which are often difficult to recognize and treat properly. It may be also secondary to other psychiatric disorders, medical diseases, or substance abuse.
|
Journal of cosmetic dermatology
| 2,020
| 12
| 0
| 8
|
30,233,077
|
Taurine protects against retinal and optic nerve damage induced by endothelin-1 in rats
|
Endothelin-1 (ET-1), a potent vasoconstrictor, is involved in retinal vascular dysregulation and oxidative stress in glaucomatous eyes. Taurine (TAU), a naturally occurring free amino acid, is known for its neuroprotective and antioxidant properties. Hence, we evaluated its neuroprotective properties against ET-1 induced retinal and optic nerve damage. ET-1 was administered intravitreally to Sprague-Dawley rats and TAU was injected as pre-, co- or post-treatment. Animals were euthanized seven days post TAU injection. Retinae and optic nerve were examined for morphology, and were also processed for caspase-3 immunostaining. Retinal redox status was estimated by measuring retinal superoxide dismutase, catalase, glutathione, and malondialdehyde levels using enzyme-linked immuosorbent assay. Histopathological examination showed significantly improved retinal and optic nerve morphology in TAU-treated groups. Morphometric examination showed that TAU pre-treatment provided marked protection against ET-1 induced damage to retina and optic nerve. In accordance with the morphological observations, immunostaining for caspase showed a significantly lesser number of apoptotic retinal cells in the TAU pre-treatment group. The retinal oxidative stress was reduced in all TAU-treated groups, and particularly in the pre-treatment group. The findings suggest that treatment with TAU, particularly pre-treatment, prevents apoptosis of retinal cells induced by ET-1 and hence prevents the changes in the morphology of retina and optic nerve. The protective effect of TAU against ET-1 induced retinal and optic nerve damage is associated with reduced retinal oxidative stress.
|
Neural regeneration research
| 2,018
| 11
| 1
| 18
|
21,124,913
|
Stimulus-specific adaptation in the auditory thalamus of the anesthetized rat.
|
The specific adaptation of neuronal responses to a repeated stimulus (Stimulus-specific adaptation, SSA), which does not fully generalize to other stimuli, provides a mechanism for emphasizing rare and potentially interesting sensory events. Previous studies have demonstrated that neurons in the auditory cortex and inferior colliculus show SSA. However, the contribution of the medial geniculate body (MGB) and its main subdivisions to SSA and detection of rare sounds remains poorly characterized. We recorded from single neurons in the MGB of anaesthetized rats while presenting a sequence composed of a rare tone presented in the context of a common tone (oddball sequences). We demonstrate that a significant percentage of neurons in MGB adapt in a stimulus-specific manner. Neurons in the medial and dorsal subdivisions showed the strongest SSA, linking this property to the non-lemniscal pathway. Some neurons in the non-lemniscal regions showed strong SSA even under extreme testing conditions (e.g., a frequency interval of 0.14 octaves combined with a stimulus onset asynchrony of 2000 ms). Some of these neurons were able to discriminate between two very close frequencies (frequency interval of 0.057 octaves), revealing evidence of hyperacuity in neurons at a subcortical level. Thus, SSA is expressed strongly in the rat auditory thalamus and contribute significantly to auditory change detection.
|
PloS one
| 2,010
| 11
| 8
| 100
|
28,545,757
|
A Randomized Clinical Trial Comparing Family-Focused Treatment and Individual Supportive Therapy for Depression in Childhood and Early Adolescence.
|
Despite the morbidity and negative outcomes associated with early-onset depression, few studies have examined the efficacy of psychosocial treatment for depressive disorders during childhood. Integrating family in treatment could have particularly salutary effects during this developmental period. This trial compared immediate posttreatment effects of family-focused treatment for childhood depression (FFT-CD) with those of individual supportive psychotherapy (IP) for children 7 to 14 years old with depressive disorders.
|
Journal of the American Academy of Child and Adolescent Psychiatry
| 2,017
| 6
| 1
| 32
|
26,431,225
|
Endocannabinoid Signaling in the Stress Response of Male and Female Songbirds.
|
Endocannabinoid (eCB) signaling plays an important role in the stress response pathways of the mammalian brain, yet its role in the avian stress response has not been described. Understanding eCB signaling in avian species (such as the European starling, Sturnus vulgaris) allows a model system that exhibits natural attenuation of hypothalamic-pituitary-adrenal (HPA) responsiveness to stressors. Specifically, seasonally breeding birds exhibit the highest HPA activity during the breeding season and subsequently exhibit a robust HPA down-regulation during molt. Because eCB signaling in mammals has an overall inhibitory effect on HPA activity, we expected shifts in eCB signaling to regulate the seasonal HPA down-regulation during molt. However, our data did not support a role for eCB signaling in the molt-related suppression of HPA activity. For example, injection of the cannabinoid receptor (CB1) antagonist, AM251, did not potentiate molt-suppressed HPA activity. Instead, our data suggest eCB regulation of HPA plasticity as birds transition from breeding to molt. In support of this hypothesis, birds in the late breeding season demonstrated a more dynamic response at the level of avian amygdala eCB content in response to acute stress. The response and directionality of this effect match that seen in mammals. Overall, our data suggest that eCB signaling may allow for a dynamic range in HPA responsiveness (eg, breeding), but the signaling pathway's role may be limited when the HPA response is restrained (eg, molt). This first characterization of eCB signaling in the avian stress response also emphasizes that although the system functions similarly to other species, its exact role may be species specific.
|
Endocrinology
| 2,015
| 12
| 0
| 4
|
18,234,110
|
Dimerization of the transmembrane domain of amyloid precursor proteins and familial Alzheimer's disease mutants.
|
Amyloid precursor protein (APP) is enzymatically cleaved by gamma-secretase to form two peptide products, either Abeta40 or the more neurotoxic Abeta42. The Abeta42/40 ratio is increased in many cases of familial Alzheimer's disease (FAD). The transmembrane domain (TM) of APP contains the known dimerization motif GXXXA. We have investigated the dimerization of both wild type and FAD mutant APP transmembrane domains.
|
BMC neuroscience
| 2,008
| 1
| 1
| 31
|
28,945,294
|
Diffusion MRI fiber tractography of the brain.
|
The ability of fiber tractography to delineate non-invasively the white matter fiber pathways of the brain raises possibilities for clinical applications and offers enormous potential for neuroscience. In the last decade, fiber tracking has become the method of choice to investigate quantitative MRI parameters in specific bundles of white matter. For neurosurgeons, it is quickly becoming an invaluable tool for the planning of surgery, allowing for visualization and localization of important white matter pathways before and even during surgery. Fiber tracking has also claimed a central role in the field of "connectomics," a technique that builds and studies comprehensive maps of the complex network of connections within the brain, and to which significant resources have been allocated worldwide. Despite its unique abilities and exciting applications, fiber tracking is not without controversy, in particular when it comes to its interpretation. As neuroscientists are eager to study the brain's connectivity, the quantification of tractography-derived "connection strengths" between distant brain regions is becoming increasingly popular. However, this practice is often frowned upon by fiber-tracking experts. In light of this controversy, this paper provides an overview of the key concepts of tractography, the technical considerations at play, and the different types of tractography algorithm, as well as the common misconceptions and mistakes that surround them. We also highlight the ongoing challenges related to fiber tracking. While recent methodological developments have vastly increased the biological accuracy of fiber tractograms, one should be aware that, even with state-of-the-art techniques, many issues that severely bias the resulting structural "connectomes" remain unresolved.
|
NMR in biomedicine
| 2,019
| 4
| 41
| 292
|
20,132,337
|
Outpatient home-based continuous intravenous dihydroergotamine therapy for intractable migraine.
|
Established consecutive-day inpatient intravenous dihydroergotamine protocols administered by bolus intravenous injection or continuous infusion injection in the hospital have demonstrated efficacy and safety in modifying the course of daily intractable headache. We conducted a study to determine efficacy, tolerability, and feasibility to treat patients with daily intractable headache with continuous intravenous dihydroergotamine in an outpatient home-based setting.
|
Headache
| 2,010
| 5
| 0
| 4
|
26,078,009
|
Morphine Modulates Interleukin-4- or Breast Cancer Cell-induced Pro-metastatic Activation of Macrophages.
|
Interactions between cancer cells and stromal cells in the tumour microenvironment play a key role in the control of invasiveness, metastasis and angiogenesis. Macrophages display a range of activation states in specific pathological contexts and alternatively activated (M2) macrophages can promote tumour aggressiveness. Opioids are able to modulate tumour growth and metastasis. We tested whether morphine modulates the activation of macrophages induced by (i) interleukin-4 (IL-4), the prototypical M2 polarization-inducing cytokine, or (ii) coculture with breast cancer cells. We showed that IL-4 causes increased MMP-9 production and expression of the alternative activation markers arginase-1 and MRC-1. Morphine prevented IL-4-induced increase in MMP-9 in a naloxone- and methylnaltrexone-reversible fashion. Morphine also prevented IL-4-elicited alternative activation of RAW264.7 macrophages. Expression of MMP-9 and arginase-1 were increased when RAW264.7 were subjected to paracrine activation by 4T1 cells, and this effect was prevented by morphine via an opioid receptor-mediated mechanism. Morphine further decreased 4T1 breast cancer cell invasion elicited by co-culture with RAW264.7. Reduction of MMP-9 expression and alternative activation of macrophages by morphine was confirmed using mouse bone marrow-derived macrophages. Taken together, our results indicate that morphine may modulate tumour aggressiveness by regulating macrophage protease production and M2 polarization within the tumour microenvironment.
|
Scientific reports
| 2,015
| 6
| 1
| 33
|
32,002,650
|
The neurological update: therapies for cerebellar ataxias in 2020.
|
Cerebellar ataxias (CAs) represent a heterogeneous group of sporadic or inherited disorders. The clinical spectrum of CAs is continuously expanding. Our understanding of the mechanisms leading to the clinical deficits has improved over these last decades, in particular thanks to progress in genetics, neuroimaging and the advent of relevant animal models allowing the identification of the pathophysiological pathways leading to CAs. The rationale behind treatments is now established for most of the CAs encountered during daily practice worldwide. In this update, we will discuss the symptomatic, physical and occupational therapies now being trialled along with individualized exercises, and present key emerging issues on immune-mediated cerebellar ataxias, hereditary cerebellar ataxias. Finally, we will discuss novel therapeutic approaches, including cerebellar non-invasive stimulation and treatments acting on RNA/proteins. So far, no state-of-the art randomized placebo-controlled clinical trial has shown a convincing clinically relevant efficacy of any drug, with the exception of 4-aminopyridine for the symptomatic treatment of episodic ataxia type 2 and downbeat nystagmus (placebo-controlled trials).
|
Journal of neurology
| 2,020
| 4
| 5
| 30
|
28,951,323
|
Preparatory cortical and spinal settings to counteract anticipated and non-anticipated perturbations.
|
Little is known about how the central nervous system prepares postural responses differently in anticipated compared to non-anticipated perturbations. To investigate this, participants were exposed to translational and rotational perturbations presented in a blocked (anticipated) and a random (non-anticipated) design. The preparatory setting ('central set') was measured by H-reflexes, motor-evoked potentials (MEPs), and short-interval intracortical inhibition (SICI) shortly before perturbation onset in the soleus of 15 healthy adults. Additionally, the behavioral consequences of differential preparatory settings were analyzed by comparing the short- (SLR), medium- (MLR), and long-latency response (LLR) of the soleus after anticipated and non-anticipated rotations and translations. H-reflexes elicited before perturbation were different between conditions (p=0.023) with larger amplitudes in anticipated translations compared to anticipated rotations (37.0%; p=0.048). Reduced SICI was found in the three conditions containing perturbations compared to static standing (p<0.001). Muscular responses assessed after perturbations remained unchanged for the SLR and MLR, whereas the LLR was decreased in anticipated rotations (-36.2%; p=0.002) and increased in anticipated translations (16.7%; p=0.046) compared to the corresponding non-anticipated perturbation. As the SLR and MLR are organized at the spinal and the LLR at the cortical level, the preparatory setting seems to mainly influence cortically mediated postural responses. However, the modulation of the H-reflex before anticipated perturbations indicates that supraspinal centers adjusted Ia-afferent transmission for the soleus in a perturbation-specific manner. Intracortical inhibition was also modulated but differentiates to a lesser extent only between perturbation conditions and unperturbed stance.
|
Neuroscience
| 2,017
| 12
| 6
| 15
|
18,717,732
|
Transient middle cerebral artery occlusion disrupts the forelimb movement representations of rat motor cortex.
|
Infarcts from proximal middle cerebral artery (MCA) stroke can produce impairments in motor function, particularly finger movements in humans and digit flexion in rats. In rats, the extent of neural damage may be limited to basal ganglia structures or may also include portions of the frontal and parietal cortex in severe cases. Although the primary motor cortex (M1) is anatomically spared in proximal MCA occlusion, its functional integrity is suspect because even a small subcortical infarct can damage neural circuits linking M1 with basal ganglia, brainstem, and spinal cord. This motivated the present study to investigate the neurophysiological integrity of M1 after transient proximal MCA occlusion. Rats, preoperatively trained and non-preoperatively trained to reach for food, received extensive reach training/testing with the contralateral-to-lesion paw for several weeks after MCA occlusion. The forelimb movement representations were assayed from the ipsilateral-to-lesion M1 with intracortical microstimulation approximately 10 weeks after MCA occlusion. Digit flexion was impaired during food grasping in rats with relatively small subcortical infarcts and was completely abolished in rats that sustained at least moderate subcortical damage. Corresponding forelimb movement representations ranged from abnormally small to absent. The results suggest that ischemia in subcortical territories of the MCA does not spare the neurophysiological properties of M1 despite its apparent anatomical intactness, probably because of damage sustained to its descending fibers. Thus, M1 dysfunction contributes to the impairments that ensue from proximal MCA occlusion, even when the infarct is limited to subcortical regions.
|
The European journal of neuroscience
| 2,008
| 9
| 0
| 7
|
22,528,871
|
Reflexive orienting by central arrows: evidence from the inattentional blindness task.
|
It was demonstrated that central arrows produce orienting of attention even when they are nonpredictive as to the target location. This finding was suggested to indicate reflexive orienting of attention by central arrows. However, it is not clear whether central arrows can produce an attentional effect without awareness. In two experiments, using a variation of the inattentional blindness task, we examine whether orienting of attention by a central arrow can be demonstrated without conscious perception of the arrow. We found that attention could be directed to the cued location even when the arrow was not consciously perceived.
|
Psychonomic bulletin & review
| 2,012
| 8
| 0
| 3
|
32,694,380
|
Identifying oxidized lipid mediators as prognostic biomarkers of chronic posttraumatic headache.
|
Chronic posttraumatic headache (PTH) is among the most common and disabling sequelae of traumatic brain injury (TBI). Current PTH treatments are often only partially effective and have problematic side effects. We previously showed in a small randomized trial of patients with chronic nontraumatic headaches that manipulation of dietary fatty acids decreased headache frequency, severity, and pain medication use. Pain reduction was associated with alterations in oxylipins derived from n-3 and n-6 fatty acids, suggesting that oxylipins could potentially mediate clinical pain reduction. The objective of this study was to investigate whether circulating oxylipins measured in the acute setting after TBI could serve as prognostic biomarkers for developing chronic PTH. Participants enrolled in the Traumatic Head Injury Neuroimaging Classification Protocol provided serum within 3 days of TBI and were followed up at 90 days postinjury with a neurobehavioral symptom inventory (NSI) and satisfaction with life survey. Liquid chromatography-tandem mass spectrometry methods profiled 39 oxylipins derived from n-3 docosahexaenoic acid (DHA), and n-6 arachidonic acid and linoleic acid. Statistical analyses assessed the association of oxylipins with headache severity (primary outcome, measured by headache question on NSI) as well as associations between oxylipins and total NSI or satisfaction with life survey scores. Among oxylipins, 4-hydroxy-DHA and 19,20-epoxy-docosapentaenoate (DHA derivatives) were inversely associated with headache severity, and 11-hydroxy-9-epoxy-octadecenoate (a linoleic acid derivative) was positively associated with headache severity. These findings support a potential for DHA-derived oxylipins as prognostic biomarkers for development of chronic PTH.
|
Pain
| 2,020
| 12
| 2
| 11
|
26,311,779
|
Temporal Structure of Neuronal Activity among Cortical Neuron Subtypes during Slow Oscillations in Anesthetized Rats.
|
Slow-wave oscillations, the predominant brain rhythm during sleep, are composed of Up/Down cycles. Depolarizing Up-states involve activity in layer 5 (L5) of the neocortex, but it is unknown how diverse subtypes of neurons within L5 participate in generating and maintaining Up-states. Here we compare the in vivo firing patterns of corticopontine (CPn) pyramidal cells, crossed-corticostriatal (CCS) pyramidal cells, and fast-spiking (FS) GABAergic neurons in the rat frontal cortex, with those of thalamocortical neurons during Up/Down cycles in the anesthetized condition. During the transition from Down- to Up-states, increased activity in these neurons was highly temporally structured, with spiking occurring first in thalamocortical neurons, followed by cortical FS cells, CCS cells, and, finally, CPn cells. Activity in some FS, CCS, and CPn neurons occurred in phase with Up-nested gamma rhythms, with FS neurons showing phase delay relative to pyramidal neurons. These results suggest that thalamic and cortical pyramidal neurons are activated in a specific temporal sequence during Up/Down cycles, but cortical pyramidal cells are activated at a similar gamma phase. In addition to Up-state firing specificity, CCS and CPn cells exhibited differences in activity during cortical desynchronization, further indicating projection- and state-dependent information processing within L5.
|
The Journal of neuroscience : the official journal of the Society for Neuroscience
| 2,015
| 8
| 0
| 13
|
20,466,399
|
[Love and neurology].
|
Love is a complex emotional state which is difficult to define. Considering anthropological studies, this feeling can now be divided into three distinct behaviors: lust, attraction for a specific partner and conjugal or filial attachment.
|
Revue neurologique
| 2,011
| 2
| 0
| 1
|
21,081,155
|
Glial cell line-derived neurotrophic factor protein content in rat skeletal muscle is altered by increased physical activity in vivo and in vitro.
|
Current evidence suggests that exercise and glial cell line-derived neurotrophic factor (GDNF) independently cause significant morphological changes in the neuromuscular system. The aim of the current study was to determine if increased physical activity regulates GDNF protein content in rat skeletal muscle. Extensor Digitorum Longus (EDL) and Soleus (SOL) hind limb skeletal muscles were analyzed following 2 weeks of involuntary exercise and 4 h of field stimulation or stretch in muscle bath preparations. GDNF protein content was measured via enzyme-linked immunosorbent assay (ELISA). Two weeks of exercise increased GDNF protein content in SOL as compared to sedentary controls (4.4±0.3 pg GDNF/mg tissue and 3.1±0.6 pg GDNF/mg tissue, respectively) and decreased GDNF protein content in EDL as compared to controls (1.0±0.1 pg GDNF/mg tissue and 2.3±0.7 pg GDNF/mg tissue, respectively). GDNF protein content in the EDL decreased following both field stimulation (56%±18% decrease from controls) and stretch (66%±10% decrease from controls). SOL responded to field stimulation with a 38%±7% increase from controls in GDNF protein content, but showed no change following stretch. Pre-treatment with α-bungarotoxin abolished the effects of field stimulation in both muscles and blocked the effect of stretch in EDL. α-bungarotoxin pre-treatment and stretch increased GDNF protein content to 240%±10% of controls in the SOL. Exposure to carbamylcholine decreased GDNF protein content to 51%±28% of controls in the EDL but not SOL. These results suggest that GDNF protein content in skeletal muscle may be controlled by stretch, where it may increase GDNF protein content, and membrane depolarization/acetylcholine (ACh) which acts to decrease GDNF protein content.
|
Neuroscience
| 2,011
| 2
| 0
| 13
|
29,925,465
|
A novel task for examining the neural basis of Theory of Mind deficits in bipolar disorder.
|
Deficits in theory of mind (ToM) processing have been observed in people with bipolar disorder (BD), but the neural basis of these deficits remains unclear. Here, we studied the relations between neural activation, dysfunctional beliefs and behavioral responses in people with BD during a second-order ToM task. Twenty-five patients and 25 healthy-control participants (HC) underwent functional magnetic resonance imaging (fMRI) while performing a novel ToM task. The Dysfunctional Attitudes scale (DAS) and the Brief Hypomanic Attitudes and Positive Predictions Inventory (BHAPPI) were used to assess dysfunctional beliefs. Significant differences in neural activation were observed between HC and BD patients in regions associated with ToM processing: medial frontal, cingulate, anterior cingulate and superior temporal gyri. Correlations between DAS scores and neural activity in medial frontal and cingulate gyri were observed for HC only. Increased activation in brain regions associated with ToM processing in patients compared to HC provides further evidence of disruption in networks controlling social-cognitive processes. Whether this results from compensatory responses to maintain appropriate behavior is unknown.
|
Psychiatry research. Neuroimaging
| 2,018
| 12
| 0
| 3
|
20,113,876
|
The influence of a chronic adolescent nicotine exposure on ethanol withdrawal severity during adulthood in C3H mice.
|
Animal and human studies have shown tolerance, consumption, relapse, and behavioral interactions between ethanol and nicotine, but little is understood about their interaction, especially as it relates to ethanol withdrawal in adulthood for subjects who have an adolescent history of using these drugs. This study investigated nicotine's influence on ethanol withdrawal seizures in two different age groups of male C3H mice. Adolescent and adult male C3H mice, beginning at postnatal day 28 or 70, respectively, were subjected to a 7-day chronic exposure to ethanol only, ethanol plus nicotine, nicotine only, or vehicle treatment. Six weeks later, all the groups were subjected to chronic exposure to ethanol vapors and the severity of their ethanol withdrawal seizures was assessed by handling-induced convulsions. An adolescent exposure to chronic nicotine resulted in an exacerbation of ethanol withdrawal seizures in adulthood. Given this, adolescence may contain a neurophysiological critical period that is sensitive to nicotine and which may result in an altered response to ethanol dependency in adulthood. These findings have serious implications for the long-term consequences following co-abuse of these drugs during adolescence.
|
Alcohol (Fayetteville, N.Y.)
| 2,010
| 2
| 0
| 3
|
33,824,392
|
RNAi efficacy is enhanced by chronic dsRNA feeding in pollen beetle.
|
Double-stranded RNAs (dsRNAs) represent a promising class of biosafe insecticidal compounds. We examined the ability to induce RNA interference (RNAi) in the pollen beetle Brassicogethes aeneus via anther feeding, and compared short-term (3 d) to chronic (17 d) feeding of various concentrations of dsRNA targeting αCOP (dsαCOP). In short-term dsαCOP feeding, only the highest concentration resulted in significant reductions in B. aeneus survival; whereas in chronic dsαCOP feeding, all three concentrations resulted in significant mortality. Chronic dsαCOP feeding also resulted in significantly greater mortality compared to short-term feeding of equivalent dsαCOP concentrations. Our results have implications for the economics and development of dsRNA spray approaches for managing crop pests, in that multiple lower-concentration dsRNA spray treatments across crop growth stages may result in greater pest management efficacy, compared to single treatments using higher dsRNA concentrations. Furthermore, our results highlight the need for research into the development of RNAi cultivars for oilseed rape protection, given the enhanced RNAi efficacy resulting from chronic, compared to short-term, dsRNA feeding in B. aeneus.
|
Communications biology
| 2,021
| 4
| 5
| 16
|
19,403,827
|
Persistent transcription- and translation-dependent long-term potentiation induced by mGluR1 in hippocampal interneurons.
|
Hippocampal interneurons synchronize the activity of large neuronal ensembles during memory consolidation. Although the latter process is manifested as increases in synaptic efficacy which require new protein synthesis in pyramidal neurons, it is unknown whether such enduring plasticity occurs in interneurons. Here, we uncover a long-term potentiation (LTP) of transmission at individual interneuron excitatory synapses which persists for at least 24 h, after repetitive activation of type-1 metabotropic glutamate receptors [mGluR1-mediated chemical late LTP (cL-LTP(mGluR1))]. cL-LTP(mGluR1) involves presynaptic and postsynaptic expression mechanisms and requires both transcription and translation via phosphoinositide 3-kinase/mammalian target of rapamycin and MAP kinase kinase-extracellular signal-regulated protein kinase signaling pathways. Moreover, cL-LTP(mGluR1) involves translational control at the level of initiation as it is prevented by hippuristanol, an inhibitor of eIF4A, and facilitated in mice lacking the cap-dependent translational repressor, 4E-BP. Our results reveal novel mechanisms of long-term synaptic plasticity that are transcription and translation-dependent in inhibitory interneurons, indicating that persistent synaptic modifications in interneuron circuits may contribute to hippocampal-dependent cognitive processes.
|
The Journal of neuroscience : the official journal of the Society for Neuroscience
| 2,009
| 4
| 1
| 17
|
28,886,358
|
Open Sesame: Open Chromatin Regions Shed Light onto Non-coding Risk Variants.
|
Human genetics and stem cell biology have advanced neurobiology for neurodevelopmental psychiatric disorders. In this issue of Cell Stem Cell, Forrest et al. (2017) demonstrate that studying the landscape of open chromatin regions in stem cell-derived neurons helps functional interpretation of non-coding genetic variants associated with these diseases.
|
Cell stem cell
| 2,017
| 9
| 0
| 4
|
27,873,219
|
Immortalization of primary microglia: a new platform to study HIV regulation in the central nervous system.
|
The major reservoirs for HIV in the CNS are in the microglia, perivascular macrophages, and to a lesser extent, astrocytes. To study the molecular events controlling HIV expression in the microglia, we developed a reliable and robust method to immortalize microglial cells from primary glia from fresh CNS tissues and commercially available frozen glial cells. Primary human cells, including cells obtained from adult brain tissue, were transformed with lentiviral vectors expressing SV40 T antigen or a combination of SVR40 T antigen and hTERT. The immortalized cells have microglia-like morphology and express key microglial surface markers including CD11b, TGFβR, and P2RY12. Importantly, these cells were confirmed to be of human origin by sequencing. The RNA expression profiles identified by RNA-seq are also characteristic of microglial cells. Furthermore, the cells demonstrate the expected migratory and phagocytic activity, and the capacity to mount an inflammatory response characteristic of primary microglia. The immortalization method has also been successfully applied to a wide range of microglia from other species (macaque, rat, and mouse). To investigate different aspects of HIV molecular regulation in CNS, the cells have been superinfected with HIV reporter viruses and latently infected clones have been selected that reactive HIV in response to inflammatory signals. The cell lines we have developed and rigorously characterized will provide an invaluable resource for the study of HIV infection in microglial cells as well as studies of microglial cell function.
|
Journal of neurovirology
| 2,017
| 2
| 9
| 72
|
20,006,675
|
Valproic acid reduces spatial working memory and cell proliferation in the hippocampus.
|
Valproic acid (VPA) is widely used clinically, as an anticonvulsant and mood stabilizer but is, however, also known to block cell proliferation through its ability to inhibit histone deacetylase enzymes. There have been a number of reports of cognitive impairments in patients taking VPA. In this investigation we examined the relationship between cognition and changes in cell proliferation within the hippocampus, a brain region where continued formation of new neurons is associated with learning and memory. Treatment of rats by i.p. injection of VPA, reduced cell proliferation in the sub granular zone of the dentate gyrus within the hippocampus. This was linked to a significant impairment in their ability to perform a hippocampus-dependent spatial memory test (novel object location). In addition, drug treatment caused a significant reduction in brain-derived neurotrophic factor (BDNF) and Notch 1 but not doublecortin levels within the hippocampus. These results support the idea that VPA may cause cognitive impairment and provide a possible mechanism for this by reducing neurogenesis within the hippocampus.
|
Neuroscience
| 2,010
| 3
| 5
| 35
|
27,791,464
|
Autophagy impairment with lysosomal and mitochondrial dysfunction is an important characteristic of oxidative stress-induced senescence.
|
Macroautophagy/autophagy has profound implications for aging. However, the true features of autophagy in the progression of aging remain to be clarified. In the present study, we explored the status of autophagic flux during the development of cell senescence induced by oxidative stress. In this system, although autophagic structures increased, the degradation of SQSTM1/p62 protein, the yellow puncta of mRFP-GFP-LC3 fluorescence and the activity of lysosomal proteolytic enzymes all decreased in senescent cells, indicating impaired autophagic flux with lysosomal dysfunction. The influence of autophagy activity on senescence development was confirmed by both positive and negative autophagy modulators; and MTOR-dependent autophagy activators, rapamycin and PP242, efficiently suppressed cellular senescence through a mechanism relevant to restoring autophagic flux. By time-phased treatment of cells with the antioxidant N-acetylcysteine (NAC), the mitochondria uncoupler carbonyl cyanide m-chlorophenyl hydrazone (CCCP) and ambroxol, a reagent with the effect of enhancing lysosomal enzyme maturation, we found that mitochondrial dysfunction plays an initiating role, while lysosomal dysfunction is more directly responsible for autophagy impairment and senescence. Interestingly, the effect of rapamycin on autophagy flux is linked to its role in functional revitalization of both mitochondrial and lysosomal functions. Together, this study demonstrates that autophagy impairment is crucial for oxidative stress-induced cell senescence, thus restoring autophagy activity could be a promising way to retard senescence.
|
Autophagy
| 2,017
| 1
| 10
| 135
|
31,730,538
|
Role of the immune system in neuropathic pain.
|
Background Acute pain is a warning mechanism that exists to prevent tissue damage, however pain can outlast its protective purpose and persist beyond injury, becoming chronic. Chronic Pain is maladaptive and needs addressing as available medicines are only partially effective and cause severe side effects. There are profound differences between acute and chronic pain. Dramatic changes occur in both peripheral and central pathways resulting in the pain system being sensitised, thereby leading to exaggerated responses to noxious stimuli (hyperalgesia) and responses to non-noxious stimuli (allodynia). Critical role for immune system cells in chronic pain Preclinical models of neuropathic pain provide evidence for a critical mechanistic role for immune cells in the chronicity of pain. Importantly, human imaging studies are consistent with preclinical findings, with glial activation evident in the brain of patients experiencing chronic pain. Indeed, immune cells are no longer considered to be passive bystanders in the nervous system; a consensus is emerging that, through their communication with neurons, they can both propagate and maintain disease states, including neuropathic pain. The focus of this review is on the plastic changes that occur under neuropathic pain conditions at the site of nerve injury, the dorsal root ganglia (DRG) and the dorsal horn of the spinal cord. At these sites both endothelial damage and increased neuronal activity result in recruitment of monocytes/macrophages (peripherally) and activation of microglia (centrally), which release mediators that lead to sensitisation of neurons thereby enabling positive feedback that sustains chronic pain. Immune system reactions to peripheral nerve injuries At the site of peripheral nerve injury following chemotherapy treatment for cancer for example, the occurrence of endothelial activation results in recruitment of CX3C chemokine receptor 1 (CX3CR1)-expressing monocytes/macrophages, which sensitise nociceptive neurons through the release of reactive oxygen species (ROS) that activate transient receptor potential ankyrin 1 (TRPA1) channels to evoke a pain response. In the DRG, neuro-immune cross talk following peripheral nerve injury is accomplished through the release of extracellular vesicles by neurons, which are engulfed by nearby macrophages. These vesicles deliver several determinants including microRNAs (miRs), with the potential to afford long-term alterations in macrophages that impact pain mechanisms. On one hand the delivery of neuron-derived miR-21 to macrophages for example, polarises these cells towards a pro-inflammatory/pro-nociceptive phenotype; on the other hand, silencing miR-21 expression in sensory neurons prevents both development of neuropathic allodynia and recruitment of macrophages in the DRG. Immune system mechanisms in the central nervous system In the dorsal horn of the spinal cord, growing evidence over the last two decades has delineated signalling pathways that mediate neuron-microglia communication such as P2X4/BDNF/GABAA, P2X7/Cathepsin S/Fractalkine/CX3CR1, and CSF-1/CSF-1R/DAP12 pathway-dependent mechanisms. Conclusions and implications Definition of the modalities by which neuron and immune cells communicate at different locations of the pain pathway under neuropathic pain states constitutes innovative biology that takes the pain field in a different direction and provides opportunities for novel approaches for the treatment of chronic pain.
|
Scandinavian journal of pain
| 2,019
| 12
| 17
| 145
|
20,706,781
|
Transfer entropy--a model-free measure of effective connectivity for the neurosciences.
|
Understanding causal relationships, or effective connectivity, between parts of the brain is of utmost importance because a large part of the brain's activity is thought to be internally generated and, hence, quantifying stimulus response relationships alone does not fully describe brain dynamics. Past efforts to determine effective connectivity mostly relied on model based approaches such as Granger causality or dynamic causal modeling. Transfer entropy (TE) is an alternative measure of effective connectivity based on information theory. TE does not require a model of the interaction and is inherently non-linear. We investigated the applicability of TE as a metric in a test for effective connectivity to electrophysiological data based on simulations and magnetoencephalography (MEG) recordings in a simple motor task. In particular, we demonstrate that TE improved the detectability of effective connectivity for non-linear interactions, and for sensor level MEG signals where linear methods are hampered by signal-cross-talk due to volume conduction.
|
Journal of computational neuroscience
| 2,011
| 2
| 15
| 164
|
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