rudyvdbrink/CitationDatabase huggingface dataset:
Targeting glutamate system for novel antipsychotic approaches: relevance for residual psychotic symptoms and treatment resistant schizophrenia.
European journal of pharmacology, 2012

Antipsychotics are the mainstay of schizophrenia treatment. However, approximately one third of schizophrenic patients do not respond or respond poorly to antipsychotics. Therefore, there is a need for new approaches that can improve schizophrenia treatment significantly. Promising strategies arise from the modulation of glutamatergic system, according to its proposed involvement in schizophrenia pathogenesis. In this review, we critically updated preclinical and clinical data on the modulation of glutamate N-methyl-D-aspartate (NMDA) receptor activity by NMDA-Rs co-agonists, glycine transporters inhibitors, AMPAkines, mGluR5 agonists, NMDA-Rs partial agonists. We focused on: 1) preclinical results in animal models mimicking the pathophysiology of psychosis, mainly believed to be responsible of negative and cognitive symptoms, and predicting antipsychotic-like activity of these compounds; and 2) clinical efficacy in open-label and double-blind trials. Albeit promising preclinical findings for virtually all compounds, clinical efficacy has not been confirmed for D-cycloserine. Contrasting evidence has been reported for glycine and D-serine, that may however have a role as add-on agents. More promising results in humans have been found for glycine transporter inhibitors. AMPAkines appear to be beneficial as pro-cognitive agents, while positive allosteric modulators of mGluR5 have not been tested in humans. Memantine has been proposed in early stages of schizophrenia, as it may counteract the effects of glutamate excitotoxicity correlated to high glutamate levels, slowing the progression of negative symptoms associated to more advanced stages of the illness.
Explicit melioration by a neural diffusion model.
Brain research, 2009

When faced with choices between two sources of reward, animals can rapidly adjust their rates of responding to each so that overall reinforcement increases. Herrnstein's 'matching law' provides a simple description of the equilibrium state of this choice allocation process: animals reallocate behavior so that relative rates of responding equal, or match, the relative rates of reinforcement obtained for each response. Herrnstein and colleagues proposed 'melioration' as a dynamical process for achieving this equilibrium, but left details of its operation unspecified. Here we examine a way of filling in the details that links the decision making and operant conditioning literatures and extends choice proportion predictions into predictions about inter-response times. Our approach implements melioration in an adaptive version of the drift diffusion model (DDM), which is widely used in decision making research to account for response time distributions. When the drift parameter of the DDM is 0 and its threshold parameters are inversely proportional to reward rates, its choice proportions dynamically track a state of exact matching. A DDM with fixed thresholds and drift that is determined by differences in reward rates can produce similar, but not identical, results. We examine the choice probability and inter-response time predictions of these models, separately and in combination, and the possible implications for brain organization provided by neural network implementations of them. Results suggest that melioration and matching may derive from synapses that estimate reward rates by a process of leaky integration, and that link together the input and output stages of a two-stage stimulus-response mechanism.
Prepubertal stress and hippocampal function: sex-specific effects.
Hippocampus, 2014

The chances of developing psychiatric disorders in adulthood are increased when stress is experienced early in life. In particular, stress experienced in the childhood or 'prepubertal' phase is associated with the later development of disorders such as depression, anxiety, post-traumatic stress disorder, and psychosis. Relatively little is known about the biological basis of this effect, but one hypothesis is that prepubertal stress produces long-lasting changes in brain development, particularly in stress sensitive regions such as the hippocampus, leaving an individual vulnerable to disorders in adulthood. In this study, we used an animal model of prepubertal stress to investigate the hypothesis that prepubertal stress induces alterations in hippocampal function in adulthood. Male and female rats were exposed to a brief, variable prepubertal stress protocol (postnatal days 25-27), and their performance in two distinct hippocampal-dependent tasks (contextual fear and spatial navigation) was compared with controls in adulthood. Prepubertal stress significantly impaired contextual fear responses in males and enhanced performance in spatial navigation in females. These results demonstrate that exposure to a brief period of stress in the prepubertal phase alters hippocampal-dependent behaviors in adulthood in a sex-specific manner.
Safety and efficacy of high-dose enteral, intravenous, and transdermal clonidine for the acute management of severe intractable childhood dystonia and status dystonicus: An illustrative case-series.
European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society, 2017

Acute dystonia in children is distressing, painful and can progress to life-threatening status dystonicus. Typical management involves benzodiazepines which can result in respiratory depression requiring PICU admission. Clonidine is less respiratory-depressant, and by facilitating sleep, switches dystonia off. It can also be administered via enteral, continuous intravenous infusion, and transdermal slow release routes. We describe the dose range and safety profile of clonidine management in a case-series of children with severe acute exacerbation of dystonia in a tertiary hospital setting.
Changes in the Excitability of Corticobulbar Projections Due to Intraoral Cooling with Ice.
Dysphagia, 2019

The aim of this study was to assess the effects of ice applied to the oral cavity on the excitability of corticobulbar projections to the swallowing muscles. The subjects were 8 healthy adult volunteers (mean age 29.0 ± 4.9 years). Motor-evoked potentials (MEPs) were recorded from the suprahyoid muscle complex using surface electrodes. Two blocks of 20 MEPs with a test stimulus intensity of 120% of the resting motor threshold were recorded at rest (baseline). Subjects then underwent 5-min thermal stimulation by either of 3 different types: (1) "ice-stick inside mouth," (2) "ice-stick on neck," and (3) "room temperature inside mouth." Blocks of 20 MEPs were then recorded immediately and at 5-min intervals for the following 15 min. There was a significant difference in the effects of the 3 interventions on the amplitude of the MEPs following stimulation (two-way ANOVA: INTERVENTION × TIME; F
Individual and situational determinants of plastic waste sorting: an experience sampling method study protocol.
BMC psychology, 2021

Plastic waste management is one of the most challenging problems of our time. Until now, only 9% of the produced plastics has been recycled. In order to increase recycling, a behavior change towards sorting of plastic waste is needed. Therefore, the main aim of the study is to gain insight in the individual and situational determinants associated with plastic waste sorting behavior. The Integrated Framework for Encouraging Pro-environmental Behaviour will be used as the theoretical framework. This framework assumes that individual egoistic and hedonic values are negatively related to pro-environmental behaviour, whereas individual biospheric and altruistic values are positively related to pro-environmental behaviour. Situational cues can activate these values, resulting in (non) pro-environmental behaviour. Taking the Integrated Framework for Encouraging Pro-environmental Behaviour into account, this study will test the hypothesized associations between individual and situational determinants and plastic waste sorting behavior, using an ecological momentary assessment approach (Experience Sampling Method, ESM).
Overexpressing temperature-sensitive dynamin decelerates phototransduction and bundles microtubules in Drosophila photoreceptors.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2009

shibire(ts1), a temperature-sensitive mutation of the Drosophila gene encoding a Dynamin orthologue, blocks vesicle endocytosis and thus synaptic transmission, at elevated, or restrictive temperatures. By targeted Gal4 expression, UAS-shibire(ts1) has been used to dissect neuronal circuits. We investigated the effects of UAS-shibire(ts1) overexpression in Drosophila photoreceptors at permissive (19 degrees C) and restrictive (31 degrees C) temperatures. At 19 degrees C, overexpression of UAS-shi(ts1) causes decelerated phototransduction and reduced neurotransmitter release. This phenotype is exacerbated with dark adaptation, age and in white mutants. Photoreceptors overexpressing UAS-shibire(ts1) contain terminals with widespread vacuolated mitochondria, reduced numbers of vesicles and bundled microtubules. Immuno-electron microscopy reveals that the latter are dynamin coated. Further, the microtubule phenotype is not restricted to photoreceptors, as UAS-shibire(ts1) overexpression in lamina cells also bundles microtubules. We conclude that dynamin has multiple functions that are interrupted by UAS-shibire(ts1) overexpression in Drosophila photoreceptors, destabilizing their neural communication irreversibly at previously reported permissive temperatures.
Mouse models of fear-related disorders: Cell-type-specific manipulations in amygdala.
Neuroscience, 2016

Fear conditioning is a model system used to study threat responses, fear memory and their dysregulation in a variety of organisms. Newly developed tools such as optogenetics, Cre recombinase and DREADD technologies have allowed researchers to manipulate anatomically or molecularly defined cell subtypes with a high degree of temporal control and determine the effect of this manipulation on behavior. These targeted molecular techniques have opened up a new appreciation for the critical contributions different subpopulations of cells make to fear behavior and potentially to treatment of fear and anxiety disorders. Here we review progress to date across a variety of techniques to understand fear-related behavior through the manipulation of different cell subtypes within the amygdala.
A Novel Dual Lentiviral CRISPR-based Transcriptional Activation System for Gene Expression Regulation in Neurons.
Bio-protocol, 2019

Robust and efficient gene expression control enables the study of a gene's function in the central nervous system. Advances in CRISPR-based technology provide new avenues not only for gene editing, but for complex transcriptional control. Here, we describe a protocol to generate high-titer lentiviruses with neuron-optimized CRISPR-activation constructs (dual lentiviruses consisting of a gene-specific single guide RNA and the CRISPR-activator) for use in primary neurons
Characterisation of amyloid-induced inflammatory responses in the rat retina.
Experimental brain research, 2011

Amyloid-induced inflammation is thought to play a critical and early role in the pathophysiology of Alzheimer's disease. As such, robust models with relevant and accessible compartments that provide a means of assessing anti-inflammatory agents are essential for the development of therapeutic agents. In the present work, we have characterised the induction of inflammation in the rat retina following intravitreal administration of amyloid-beta protein (Aβ). Histology and mRNA endpoints in the retina demonstrate Aβ1-42-, but not Aβ42-1-, induced inflammatory responses characterised by increases in markers for microglia and astrocytes (ionised calcium-binding adaptor molecule 1 (iba-1), GFAP and nestin) and increases in mRNA for inflammatory cytokines and chemokines such as IL1-β, MIP1α and TNFα. Likewise, analysis of vitreal cytokines also revealed increases in inflammatory cytokines and chemokines, including IL1-β, MIP1α and MCP1, induced by Aβ1-42 but not Aβ42-1. This profile of pro-inflammatory gene and protein expression is consistent with that observed in the Alzheimer's disease brain and suggest that this preclinical model may provide a useful relevant tool in the development of anti-inflammatory approaches directed towards Alzheimer's disease therapy.
Cutting a long story short: reaction times in acute stroke are associated with longer term cognitive outcomes.
Journal of the neurological sciences, 2012

The viability and usefulness of cognitive assessment in acute stroke have been questioned, with practical challenges arising from the focal nature of neurological deficits as well as heterogeneity in arousal state. We aimed to test whether acute measures of attention correlate with attentional function at 3 months post-stroke.
Decoding ventromedial hypothalamic neural activity during male mouse aggression.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014

The ventromedial hypothalamus, ventrolateral area (VMHvl) was identified recently as a critical locus for inter-male aggression. Optogenetic stimulation of VMHvl in male mice evokes attack toward conspecifics and inactivation of the region inhibits natural aggression, yet very little is known about its underlying neural activity. To understand its role in promoting aggression, we recorded and analyzed neural activity in the VMHvl in response to a wide range of social and nonsocial stimuli. Although response profiles of VMHvl neurons are complex and heterogeneous, we identified a subpopulation of neurons that respond maximally during investigation and attack of male conspecific mice and during investigation of a source of male mouse urine. These "male responsive" neurons in the VMHvl are tuned to both the inter-male distance and the animal's velocity during attack. Additionally, VMHvl activity predicts several parameters of future aggressive action, including the latency and duration of the next attack. Linear regression analysis further demonstrates that aggression-specific parameters, such as distance, movement velocity, and attack latency, can model ongoing VMHvl activity fluctuation during inter-male encounters. These results represent the first effort to understand the hypothalamic neural activity during social behaviors using quantitative tools and suggest an important role for the VMHvl in encoding movement, sensory, and motivation-related signals.
Surgical Treatment of Vestibular Schwannoma: Does Age Matter?
World neurosurgery, 2016

For older patients (>65 years) who undergo surgical treatment of vestibular schwannoma (VS), the reported rates of facial nerve preservation, hearing preservation, and complications are inconsistent. Many surgeons believe that older patients have worse outcomes than their younger counterparts and advise against surgical treatment. We analyzed a consecutive series of patients with VS treated with surgery to determine whether age was a factor in outcome.
Maternal IL-6 during pregnancy can be estimated from newborn brain connectivity and predicts future working memory in offspring.
Nature neuroscience, 2018

Several lines of evidence support the link between maternal inflammation during pregnancy and increased likelihood of neurodevelopmental and psychiatric disorders in offspring. This longitudinal study seeks to advance understanding regarding implications of systemic maternal inflammation during pregnancy, indexed by plasma interleukin-6 (IL-6) concentrations, for large-scale brain system development and emerging executive function skills in offspring. We assessed maternal IL-6 during pregnancy, functional magnetic resonance imaging acquired in neonates, and working memory (an important component of executive function) at 2 years of age. Functional connectivity within and between multiple neonatal brain networks can be modeled to estimate maternal IL-6 concentrations during pregnancy. Brain regions heavily weighted in these models overlap substantially with those supporting working memory in a large meta-analysis. Maternal IL-6 also directly accounts for a portion of the variance of working memory at 2 years of age. Findings highlight the association of maternal inflammation during pregnancy with the developing functional architecture of the brain and emerging executive function.
Heterologous Expression, Biosynthetic Studies, and Ecological Function of the Selective Gq-Signaling Inhibitor FR900359.
Angewandte Chemie (International ed. in English), 2018

The cyclic depsipeptide FR900359 (FR), isolated from the tropical plant Ardisia crenata, is a strong and selective inhibitor of Gq proteins, making it an indispensable pharmacological tool to study Gq-related processes, as well as a promising drug candidate. Gq inhibition is a novel mode of action for defense chemicals and crucial for the ecological function of FR, as shown by in vivo experiments in mice, its affinity to insect Gq proteins, and insect toxicity studies. The uncultured endosymbiont of A. crenata was sequenced, revealing the FR nonribosomal peptide synthetase (frs) gene cluster. We here provide a detailed model of FR biosynthesis, supported by in vitro enzymatic and bioinformatic studies, and the novel analogue AC-1, which demonstrates the flexibility of the FR starter condensation domains. Finally, expression of the frs genes in E. coli led to heterologous FR production in a cultivable, bacterial host for the first time.
Integrative approach to sporadic Alzheimer's disease: deficiency of TYROBP in a tauopathy mouse model reduces C1q and normalizes clinical phenotype while increasing spread and state of phosphorylation of tau.
Molecular psychiatry, 2019

TYROBP/DAP12 forms complexes with ectodomains of immune receptors (TREM2, SIRPβ1, CR3) associated with Alzheimer's disease (AD) and is a network hub and driver in the complement subnetwork identified by multi-scale gene network studies of postmortem human AD brain. Using transgenic or viral approaches, we characterized in mice the effects of TYROBP deficiency on the phenotypic and pathological evolution of tauopathy. Biomarkers usually associated with worsening clinical phenotype (i.e., hyperphosphorylation and increased tauopathy spreading) were unexpectedly increased in MAPT
Disparity-specific spatial interactions: evidence from EEG source imaging.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012

Using cortical source estimation techniques based on high-density EEG and fMRI measurements in humans, we measured how a disparity-defined surround influenced the responses to the changing disparity of a central disk within five visual ROIs: V1, V4, lateral occipital complex (LOC), hMT+, and V3A. The responses in the V1 ROI were not consistently affected either by changes in the characteristics of the surround (correlated or uncorrelated) or by its disparity value, consistent with V1 being responsive only to absolute, not relative, disparity. Correlation in the surround increased the responses in the V4, LOC, and hMT+ ROIs over those measured with the uncorrelated surround. Thus, these extrastriate areas contain neurons that are sensitive to disparity differences. However, their evoked responses did not vary systematically with the surround disparity. Responses in the V3A ROI, in contrast, were increased by correlation in the surround and varied with its disparity. We modeled these V3A responses as attributable to a gain modulation of the absolute disparity response, where the gain amplitude is proportional to the center-surround disparity difference. An additional experiment identified a nonlinear center-surround interaction in V3A that facilitates the responses when center and surround are misaligned but suppresses it when they share the same disparity plane.
The correlation between reading and mathematics ability at age twelve has a substantial genetic component.
Nature communications, 2014

Dissecting how genetic and environmental influences impact on learning is helpful for maximizing numeracy and literacy. Here we show, using twin and genome-wide analysis, that there is a substantial genetic component to children's ability in reading and mathematics, and estimate that around one half of the observed correlation in these traits is due to shared genetic effects (so-called Generalist Genes). Thus, our results highlight the potential role of the learning environment in contributing to differences in a child's cognitive abilities at age twelve.
The glutaminergic, GABAergic, dopaminergic but not cholinergic neurons are susceptible to anaesthesia-induced cell death in the rat developing brain.
Neuroscience, 2011

Neuronal cell death induced by anaesthetics in the developing brain was evident in previous pre-clinical studies. However, the neuronal cell types involved in anaesthesia-induced neuronal cell death remains elusive. The aim of this study was to investigate glutamatergic, GABAergic, cholinergic and dopaminergic neuronal cell apoptosis induced by anaesthetic exposure in specific brain regions in rats. Separate cohorts of 7-day-old Sprague Dawley (SD) rat pups were randomly assigned to two groups: Naive and anaesthetics alone (70% nitrous oxide and 0.75% isoflurane exposure for 6 h). The brains were sectioned and the slices that contained the basal forebrain, substantia nigra, cornu ammonis area 1 (CA1) subarea of hippocampus or cingulate cortex were selected and subsequently subjected to double-labelled fluorescent immunohistochemistry for choline acetyltransferase, dopamine, vesicular glutamate transporter 1 (vGLUT1) or glutamic acid decarboxylase 67 (GAD67) together with caspase 3, respectively. Compared to the naive control, anaesthetic exposure significantly increased the number of caspase-3 positive cells in the CA1 subarea of hippocampus, cingulate cortex, and substantia nigra, but not in the basal forebrain. 54% and 14% of apoptotic cells in the CA1 subarea of hippocampus were GABAergic and glutamatergic neurons respectively. In the cingulate cortex, 30% and 37% of apoptotic cells were GABAergic and glutamatergic neurons respectively. In the substantia nigra, 22% of apoptotic cells were dopaminergic neurons. Our data suggests, anaesthetic exposure significantly increases neuroapoptosis of glutamatergic, GABAergic and dopaminergic neurons in the developing brain but not that of the cholinergic neurons in the basal forebrain.
Extracellular truncated tau causes early presynaptic dysfunction associated with Alzheimer's disease and other tauopathies.
Oncotarget, 2017

The largest part of tau secreted from AD nerve terminals and released in cerebral spinal fluid (CSF) is C-terminally truncated, soluble and unaggregated supporting potential extracellular role(s) of NH
DARK Classics in Chemical Neuroscience: Cocaine.
ACS chemical neuroscience, 2018

In this Review, we consider the story of cocaine from its humble origins in South America to its status as one of the most abused substances in 21st century society. The synthesis and biosynthesis of cocaine are discussed, as well as its pharmacokinetics, metabolism, pharmacology, and importance in modern neuroscience and molecular imaging.