rudyvdbrink/CitationDatabase huggingface dataset:
Effects of maternal separation, early handling, and gonadal sex on regional metabolic capacity of the preweanling rat brain.
Brain research, 2011

This is the first study to assess the effects of mother-infant separation on regional metabolic capacity in the preweanling rat brain. Mother-infant separation is generally known to be stressful for rat pups. Holtzman adolescent rats show a depressive-like behavioral phenotype after maternal separation during the preweanling period. However, information is lacking on the effects of maternal separation on the brains of rat pups. We addressed this issue by mapping the brains of preweanling Holtzman rat pups using cytochrome oxidase histochemistry, which reflects long-term changes in brain metabolic capacity, following two weeks of repeated, prolonged maternal separation, and compared this to both early handled and non-handled pups. Quantitative image analysis revealed that maternal separation reduced cytochrome oxidase activity in the medial prefrontal cortex and nucleus accumbens shell. Maternal separation reduced prefrontal cytochrome oxidase to a greater degree in female pups than in males. Early handling reduced cytochrome oxidase activity in the posterior parietal cortex, ventral tegmental area, and subiculum, but increased cytochrome oxidase activity in the lateral frontal cortex. The sex-dependent effects of early handling on cytochrome oxidase activity were limited to the medial prefrontal cortex. Regardless of separation group, females had greater cytochrome oxidase activity in the habenula and ventral tegmental area compared to males. These findings suggest that early life mother-infant separation results in dysfunction of prefrontal and mesolimbic regions in the preweanling rat brain that may contribute to behavioral changes later in life.
Does hypnotic susceptibility influence information processing speed and motor cortical preparatory activity?
Neuropsychologia, 2019

Responsiveness to suggestions while hypnotized is termed hypnotic susceptibility. An association between reaction time and hypnotic susceptibility has been demonstrated, but whether distinct changes in brain activity accompany this relationship remains unclear. We investigated the effect of hypnotic susceptibility on the speed of information processing and motor cortical preparatory activity. Twenty-one "low" (Low
Downregulation of Spermine Augments Dendritic Persistent Sodium Currents and Synaptic Integration after Status Epilepticus.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2015

Dendritic voltage-gated ion channels profoundly shape the integrative properties of neuronal dendrites. In epilepsy, numerous changes in dendritic ion channels have been described, all of them due to either their altered transcription or phosphorylation. In pilocarpine-treated chronically epileptic rats, we describe a novel mechanism that causes an increased proximal dendritic persistent Na(+) current (INaP). We demonstrate using a combination of electrophysiology and molecular approaches that the upregulation of dendritic INaP is due to a relief from polyamine-dependent inhibition. The polyamine deficit in hippocampal neurons is likely caused by an upregulation of the degrading enzyme spermidine/spermine acetyltransferase. Multiphoton glutamate uncaging experiments revealed that the increase in dendritic INaP causes augmented dendritic summation of excitatory inputs. These results establish a novel post-transcriptional modification of ion channels in chronic epilepsy and may provide a novel avenue for treatment of temporal lobe epilepsy.
Peritoneal macrophage from male and female SJL mice differ in IL-10 expression and macrophage maturation.
Journal of leukocyte biology, 2012

Injection of proteins and particulate antigens into the peritoneal cavity of male SJL mice preferentially activates T cells secreting Th2 cytokines. Identical immunizations of females activate T cells secreting Th1 cytokines. CD11b(+)F4/80(hi) LPM and CD11b(+)F4/80(lo) SPM populations were compared between naive males and females to define their role in supporting differential Th1 versus Th2 T cell activation. No sex-dependent differences in the expression of MHC class II, costimulatory molecules, and MR were detected. Immunization induced influx of CD11b(lo)F4/80(lo) cells in both sexes. CD11b(lo)F4/80(lo) cells consist predominantly of Ly6C(hi) monocytes, which mature into a Ly6C(-) SPM subset. Following immunization, equivalent frequencies of LPM had taken up antigen. However, the CD11b(lo)F4/80(lo) population, which had taken up antigen, was decreased significantly in males compared with females. Similar to naïve macrophages, antigen-positive cells in immunized males and females exhibited no phenotypic differences. However, fewer Ly6C(-)F4/80(+) cells were present in males compared with females, consistent with the reduced number of antigen-positive cells. Furthermore, CD11b(lo)F4/80(lo) cells, which had taken up antigen in males, expressed increased IL-10 and limited IL-12 mRNA compared with the predominant IL-12 mRNA expression in female-derived, antigen-positive CD11b(lo)F4/80(lo) cells. IL-10 blockade increased the frequency of Ly6C(-)F4/80(+) cells in males to the frequency in females, suggesting that preferential activation of Th2 T cells in male SJL mice is associated with increased IL-10 expression and limited antigen presentation as a result of decreased macrophage maturation under the influence of IL-10.
The immediate early gene arc/arg3.1: regulation, mechanisms, and function.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2008

In a manner unique among activity-regulated immediate early genes (IEGs), mRNA encoded by Arc (also known as Arg3.1) undergoes rapid transport to dendrites and local synaptic translation. Despite this intrinsic appeal, relatively little is known about the neuronal and behavioral functions of Arc or its molecular mechanisms of action. Here, we attempt to distill recent advances on Arc spanning its transcriptional and translational regulation, the functions of the Arc protein in multiple forms of neuronal plasticity [long-term potentiation (LTP), long-term depression (LTD), and homeostatic plasticity], and its broader role in neural networks of behaving animals. Worley and colleagues have shown that Arc interacts with endophilin and dynamin, creating a postsynaptic trafficking endosome that selectively modifies the expression of AMPA-type glutamate receptors at the excitatory synapses. Both LTD and homeostatic plasticity in the hippocampus are critically dependent on Arc-mediated endocytosis of AMPA receptors. LTD evoked by activation of metabotropic glutamate receptors depends on rapid Arc translation controlled by elongation factor 2. Bramham and colleagues have shown that sustained translation of newly induced Arc mRNA is necessary for cofilin phosphorylation and stable expansion of the F-actin cytoskeleton underlying LTP consolidation in the dentate gyrus of live rats. In addition to regulating F-actin, Arc synthesis maintains the activity of key translation factors during LTP consolidation. This process of Arc-dependent consolidation is activated by the secretory neurotrophin, BDNF. Moore and colleagues have shown that Arc mRNA is a natural target for nonsense-mediated mRNA decay (NMD) by virtue of its two conserved 3'-UTR introns. NMD and other related translation-dependent mRNA decay mechanisms may serve as critical brakes on protein expression that contribute to the fine spatial-temporal control of Arc synthesis. In studies in behaving rats, Guzowski and colleagues have shown that location-specific firing of CA3 and CA1 hippocampal neurons in the presence of theta rhythm provides the necessary stimuli for activation of Arc transcription. The impact of Arc transcription in memory processes may depend on the specific context of coexpressed IEGs, in addition to posttranscriptional regulation of Arc by neuromodulatory inputs from the amygdala and other brain regions. In sum, Arc is emerging as a versatile, finely tuned system capable of coupling changes in neuronal activity patterns to diverse forms of synaptic plasticity, thereby optimizing information storage in active networks.
Sitting time, physical fitness impairments and metabolic abnormalities in people with bipolar disorder: An exploratory study.
Psychiatry research, 2016

A sedentary lifestyle is an independent risk factor for cardiovascular disease and mortality. Little is known however about sedentary behavior in people with bipolar disorder (BD). The primary aim of this study was to explore associations between sitting time (as a proxy for a sedentary lifestyle) and physical fitness and metabolic parameters in BD. A secondary aim was to investigate associations between psychiatric symptoms, psychotropic medication use and sitting time. Thirty-nine (21♀) participants (43.7±12.4 years) completed a full metabolic screening, the sitting time item of the International Physical Activity Questionnaire, the Quick Inventory of Depressive Symptomatology self-report and the Hypomania Checklist-32. Additionally participants performed the Eurofit-test battery and 6-min walk test. The mean time spent sitting per day for the entire sample was 7.0±3.0h. A higher body mass index, worse physical fitness and higher antipsychotic medication dose were identified as independent predictors of higher levels of sitting behavior. The model explained 76.5% of the variability in the sitting time. Given that a sedentary lifestyle is an independent predictor of cardiovascular disease, future interventions specifically targeting time spend sitting are warranted in BD, with a particular emphasis on those with high body mass index and low fitness levels.
Epigenetics insights into chronic pain: DNA hypomethylation in fibromyalgia-a controlled pilot-study.
Pain, 2017

To evaluate changes in DNA methylation profiles in patients with fibromyalgia (FM) compared to matched healthy controls (HCs). All individuals underwent full clinical and neurophysiological assessment by cortical excitability (CE) parameters measured by transcranial magnetic stimulation. DNA from the peripheral blood of patients with FM (n = 24) and HC (n = 24) were assessed using the Illumina-HumanMethylation450 BeadChips. We identified 1610 differentially methylated positions (DMPs) in patients with FM displaying a nonrandom distribution in regions of the genome. Sixty-nine percent of DMP in FM were hypomethylated compared to HC. Differentially methylated positions were enriched in 5 genomic regions (1p34; 6p21; 10q26; 17q25; 19q13). The functional characterization of 960 genes related to DMPs revealed an enrichment for MAPK signaling pathway (n = 18 genes), regulation of actin cytoskeleton (n = 15 genes), and focal adhesion (n = 13 genes). A gene-gene interaction network enrichment analysis revealed the participation of DNA repair pathways, mitochondria-related processes, and synaptic signaling. Even though DNA was extracted from peripheral blood, this set of genes was enriched for disorders such as schizophrenia, mood disorders, bulimia, hyperphagia, and obesity. Remarkably, the hierarchical clusterization based on the methylation levels of the 1610 DMPs showed an association with neurophysiological measurements of CE in FM and HC. Fibromyalgia has a hypomethylation DNA pattern, which is enriched in genes implicated in stress response and DNA repair/free radical clearance. These changes occurred parallel to changes in CE parameters. New epigenetic insights into the pathophysiology of FM may provide the basis for the development of biomarkers of this disorder.
Resting-state functional connectivity in drug-naive pediatric patients with Tourette syndrome and obsessive-compulsive disorder.
Journal of psychiatric research, 2020

Previous studies in cohorts of Tourette syndrome (TS) or obsessive-compulsive disorder (OCD) patients have not clarified whether these two disorders represent two clinical conditions or they are distinct clinical phenotypes of a common disease spectrum. The study aimed to compare functional connectivity (FC) patterns in a pediatric drug-naive cohort of 16 TS patients without any comorbidity (TS), 14 TS patients with OCD (TS + OCD), and 10 pure OCD patients as well as 11 matched controls that underwent resting state fMRI. Via independent component analysis, we examined FC in the basal ganglia (BGN), sensorimotor (SMN), cerebellum (CBN), frontoparietal (FPN), default-mode (DMN), orbitofrontal (OBFN), and salience (SAN) networks among the above cohorts and their association with clinical measures. Compared to controls, TS and TS + OCD patients showed higher FC in the BGN, SMN, CBN and DMN and lower FC in the FPN and SAN. The TS and TS + OCD groups showed comparable FC in all networks. In contrast to controls, OCD patients exhibited increased FC in the BGN, SMN, CBN, DMN, FPN, and SAN. OCD patients also showed higher FC in CBN and FPN when compared with TS and TS + OCD patients both separately and as one group. Tic severity negatively correlated with FC in CBN and FPN in the TS group, while the compulsiveness scores positively correlated with the same two networks in OCD patients. Our findings suggest common FC changes in TS and TS + OCD patients. In contrast, OCD is characterized by a distinctive pattern of FC changes prominently involving the CBN and FPN.
Feature head-start: Conjunction search following progressive feature disclosure.
Vision research, 2009

When a colour/orientation conjunction search display is immediately preceded by a display that shows either the colour or the orientation of each upcoming search item, search is faster after colour-preview than after orientation-preview. One explanation for this feature asymmetry is that colour has priority access to attentional selection relative to features such as orientation and size. In support of this hypothesis, we show that this asymmetry persists even after colour and orientation feature search performance is equated. However, this notion was ruled out by our subsequent experiments in which the target was defined by conjunction of colour and size; colour-preview was less helpful than size-preview (even though colour-feature search was faster than size-feature search, for these feature values). A final set of experiments tested size-preview vs. orientation-preview for size/orientation conjunction search, using stimuli for which orientation-feature search was easier than size-feature search. Size-preview produced much faster search than orientation-preview, demonstrating again that ease of feature search does not predict effects of a feature-preview. Overall, size produced the most facilitation when presented as a feature-preview (for both colour/size and size/orientation conjunctions), followed by colour (for colour/orientation conjunction but not for colour/size conjunction) and then orientation (which never facilitated search). Whilst each feature-preview may potentially facilitate search, the transition from feature-preview display to search display could disrupt search processes, because of luminance and/or colour changes. We see evidence for some sort of disruption when the feature-preview slows search. An explanation of this set of results must focus on both facilitation and disruption: these effects are not mutually exclusive, and neither suffices alone, since performance after feature-preview can be significantly better or significantly worse than conjunction baseline.
What the orbitofrontal cortex does not do.
Nature neuroscience, 2015

The number of papers about the orbitofrontal cortex (OFC) has grown from 1 per month in 1987 to a current rate of over 50 per month. This publication stream has implicated the OFC in nearly every function known to cognitive neuroscience and in most neuropsychiatric diseases. However, new ideas about OFC function are typically based on limited data sets and often ignore or minimize competing ideas or contradictory findings. Yet true progress in our understanding of an area's function comes as much from invalidating existing ideas as proposing new ones. Here we consider the proposed roles for OFC, critically examining the level of support for these claims and highlighting the data that call them into question.
Hearing requires otoferlin-dependent efficient replenishment of synaptic vesicles in hair cells.
Nature neuroscience, 2010

Inner hair cell ribbon synapses indefatigably transmit acoustic information. The proteins mediating their fast vesicle replenishment (hundreds of vesicles per s) are unknown. We found that an aspartate to glycine substitution in the C(2)F domain of the synaptic vesicle protein otoferlin impaired hearing by reducing vesicle replenishment in the pachanga mouse model of human deafness DFNB9. In vitro estimates of vesicle docking, the readily releasable vesicle pool (RRP), Ca(2+) signaling and vesicle fusion were normal. Moreover, we observed postsynaptic excitatory currents of variable size and spike generation. However, mutant active zones replenished vesicles at lower rates than wild-type ones and sound-evoked spiking in auditory neurons was sparse and only partially improved during longer interstimulus intervals. We conclude that replenishment does not match the release of vesicles at mutant active zones in vivo and a sufficient standing RRP therefore cannot be maintained. We propose that otoferlin is involved in replenishing synaptic vesicles.
VGF and its C-terminal peptide TLQP-62 in ventromedial prefrontal cortex regulate depression-related behaviors and the response to ketamine.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2019

Patients with major depressive disorder (MDD) often have structural and functional deficits in the ventromedial prefrontal cortex (vmPFC), but the underlying molecular pathways are incompletely understood. The neuropeptide precursor VGF (non-acronymic) plays a critical role in depression and antidepressant efficacy in hippocampus and nucleus accumbens, however its function in vmPFC has not been investigated. Here, we show that VGF levels were reduced in Brodmann area 25 (a portion of human vmPFC) of MDD patients and in mouse vmPFC following chronic restraint stress (CRS), and were increased by ketamine in mouse vmPFC. VGF overexpression in vmPFC prevented behavioral deficits induced by CRS, and VGF knockdown in vmPFC increased susceptibility to subchronic variable stress (SCVS) and reduced ketamine's antidepressant efficacy. Acute intra-vmPFC TLQP-62 infusion induced behavioral phenotypes that mimic those produced by antidepressant drug treatment. These antidepressant-like effects were sustained for 7 days and were abolished by local Bdnf gene ablation, or pretreatment with xestospongin C, an inhibitor of IP
Companion Animals Symposium: Environmental enrichment for companion, exotic, and laboratory animals.
Journal of animal science, 2011

Animal scientists have an extraordinary burden to promote the health and well-being of all animals in their care. Promoting species- or breed-appropriate behaviors through proper training and enrichment, regardless of animal housing, should be a paramount concern for all animal scientists working with exotic animals, laboratory animals, shelter animals, or privately owned pet animals. Developing ideal training and enrichment programs for any species begins with understanding basic behavior patterns and emotional systems of animals. The basic emotional systems in mammals have been extensively mapped; however, most of these studies are in the neuroscience literature and seldom read by animal science professionals. The emotional circuits for fear have been well documented through studies demonstrating that lesions to the amygdala will block both conditioned and unconditioned fear behaviors. Additionally, other core emotional systems including seeking (i.e., approaching a novel stimulus), rage, panic (e.g., separation stress), play, lust (i.e., sex drive), and care (e.g., mother-young nurturing behavior) have been identified. More recent neuroscience research has discovered the subcortical brain regions that drive different types of seeking behaviors. Research to increase the understanding of the emotional systems that drive both abnormal and normal animal behaviors could greatly improve animal welfare by making it possible to provide more effective environmental enrichment programs. Enrichment devices and methods could be specifically designed to enable the expression of highly motivated behaviors that are driven by emotional circuits in the brain. The objective of this paper is to increase awareness of animal scientists to the field of neuroscience studying animal emotions and the application of that science to improve the welfare of captive exotic animals, laboratory animals, and pets with environmental enrichment.
AMPA receptor and metabotropic glutamate receptor 1 adaptations in the nucleus accumbens core during incubation of methamphetamine craving.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2019

Cue-induced drug craving progressively intensifies after withdrawal from self-administration of cocaine, methamphetamine, and other drugs of abuse, a phenomenon termed incubation of craving. For cocaine and methamphetamine, expression of incubated craving ultimately depends on strengthening of nucleus accumbens (NAc) synapses through an accumulation of high conductance Ca
Intravascular Ultrasound in Carotid Web.
Journal of neurointerventional surgery, 2020

Carotid web (CaW) is a shelf-like linear filling defect in the posterior aspect of the internal carotid bulb, representing an intimal variant of fibromuscular dysplasia. The diagnosis of CaW is traditionally restricted to digital subtraction angiography (DSA), CT/MR angiography (CTA/MRA), and Duplex ultrasonography. In this series of patients with acute ischemic stroke, we evaluated the potential utility of intravascular ultrasound (IVUS) in further characterizing suspected CaWs.
Do blind cavefish have behavioral specializations for active flow-sensing?
Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology, 2011

Blind cavefish use a form of active sensing in which burst-coast swimming motions generate flow signals detected by the lateral line. To determine if blind cavefish have evolved behavioral specializations for active flow-sensing, including the ability to regulate flow signal production through lateral line feedback, the swimming kinematics of blind and sighted morphs of Astyanax were compared before and after 24 h of familiarization with a novel, dark environment and with and without lateral line functionality. Although both morphs showed little difference in the vast majority of kinematic parameters measured, blind morphs differed significantly from sighted morphs in having a much higher incidence of swim cycle sequences devoid of sharp turns. Both lateral line deprivation and familiarization with the arena led to significant declines in this number for blind, but not sighted morphs. These findings suggest that swimming kinematics are largely conserved, but that blind morphs have nevertheless evolved enhanced abilities to use lateral line feedback when linking swim cycles into continuous, straight trajectories for exploratory purposes. This behavioral specialization can best be understood in terms of the intermittent and short-range limitations of active flow-sensing and the challenges they pose for spatial orientation and navigation.