rudyvdbrink/CitationDatabase huggingface dataset:
qKAT: Quantitative Semi-automated Typing of Killer-cell Immunoglobulin-like Receptor Genes.
Journal of visualized experiments : JoVE, 2019

Killer cell immunoglobulin-like receptors (KIRs) are a set of inhibitory and activating immune receptors, on natural killer (NK) and T cells, encoded by a polymorphic cluster of genes on chromosome 19. Their best-characterized ligands are the human leukocyte antigen (HLA) molecules that are encoded within the major histocompatibility complex (MHC) locus on chromosome 6. There is substantial evidence that they play a significant role in immunity, reproduction, and transplantation, making it crucial to have techniques that can accurately genotype them. However, high-sequence homology, as well as allelic and copy number variation, make it difficult to design methods that can accurately and efficiently genotype all KIR genes. Traditional methods are usually limited in the resolution of data obtained, throughput, cost-effectiveness, and the time taken for setting up and running the experiments. We describe a method called quantitative KIR semi-automated typing (qKAT), which is a high-throughput multiplex real-time polymerase chain reaction method that can determine the gene copy numbers for all genes in the KIR locus. qKAT is a simple high-throughput method that can provide high-resolution KIR copy number data, which can be further used to infer the variations in the structurally polymorphic haplotypes that encompass them. This copy number and haplotype data can be beneficial for studies on large-scale disease associations, population genetics, as well as investigations on expression and functional interactions between KIR and HLA.
Long-term accumulation of microglia with proneurogenic phenotype concomitant with persistent neurogenesis in adult subventricular zone after stroke.
Glia, 2009

Neural stem cells (NSCs) in the adult rat subventricular zone (SVZ) generate new striatal neurons during several months after ischemic stroke. Whether the microglial response associated with ischemic injury extends into SVZ and influences neuroblast production is unknown. Here, we demonstrate increased numbers of activated microglia in ipsilateral SVZ concomitant with neuroblast migration into the striatum at 2, 6, and 16 weeks, with maximum at 6 weeks, following 2 h middle cerebral artery occlusion in rats. In the peri-infarct striatum, numbers of activated microglia peaked already at 2 weeks and declined thereafter. Microglia in SVZ were resident or originated from bone marrow, with maximum proliferation during the first 2 weeks postinsult. In SVZ, microglia exhibited ramified or intermediate morphology, signifying a downregulated inflammatory profile, whereas amoeboid or round phagocytic microglia were frequent in the peri-infarct striatum. Numbers of microglia expressing markers of antigen-presenting cells (MHC-II, CD86) increased in SVZ but very few lymphocytes were detected. Using quantitative PCR, strong short- and long-term increase (at 1 and 6 weeks postinfarct) of insulin-like growth factor-1 (IGF-1) gene expression was detected in SVZ tissue. Elevated numbers of IGF-1-expressing microglia were found in SVZ at 2, 6, and 16 weeks after stroke. At 16 weeks, 5% of microglia but no other cells in SVZ expressed the IGF-1 protein, which mitigates apoptosis and promotes proliferation and differentiation of NSCs. The long-term accumulation of microglia with proneurogenic phenotype in the SVZ implies a supportive role of these cells for the continuous neurogenesis after stroke.
Purinergic receptor antagonists inhibit odorant-mediated CREB phosphorylation in sustentacular cells of mouse olfactory epithelium.
BMC neuroscience, 2011

Extracellular nucleotides have long been known to play neuromodulatory roles and to be involved in intercellular signalling. In the olfactory system, ATP is released by olfactory neurons, and exogenous ATP can evoke an increase in intracellular calcium concentration in sustentacular cells, the nonneuronal supporting cells of the olfactory epithelium. Here we investigate the hypothesis that olfactory neurons communicate with sustentacular cells via extracellular ATP and purinergic receptor activation.
A new psychometric questionnaire for reporting of somatosensory percepts.
Journal of neural engineering, 2018

There have been remarkable advances over the past decade in neural prostheses to restore lost motor function. However, restoration of somatosensory feedback, which is essential for fine motor control and user acceptance, has lagged behind. With an increasing interest in using electrical stimulation to restore somatosensory sensations within the peripheral (PNS) and central nervous systems (CNS), it is critical to characterize the percepts evoked by electrical stimulation in a standardized manner with a validated psychometric questionnaire. This will allow comparison of results from applications at various nervous system levels in multiple settings.
Differences between dextroamphetamine and methamphetamine: behavioral changes and oxidative damage in brain of Wistar rats.
Journal of neural transmission (Vienna, Austria : 1996), 2012

In this study methamphetamine (m-AMPH) and dextroamphetamine (d-AMPH) were compared to determine the potency of the two drugs on behavior and oxidative damage in brain of rats. Male adult Wistar rats were given single (acute administration) or repeated (chronic administration, 14 days) intraperitoneal injections of saline (0.9% NaCl), d-AMPH (2 mg/kg) or m-AMPH (0.25, 0.5, 1 or 2 mg/kg). Locomotor activity was evaluated in open-field apparatus 2 h after the last drug injection. Additionally, thiobarbituric acid reactive substances (TBARS) and protein carbonyl formation were measured in the prefrontal cortex, amygdala, hippocampus and striatum. In both experiments, d-AMPH and m-AMPH (all doses administered) increased the locomotor activity of animals, meantime, no significant difference between d-AMPH and m-AMPH was observed. d-AMPH and m-AMPH increased lipid and protein damage, but m-AMPH was more potent than d-AMPH, however, this effect varies depending on the brain region and the experimental protocol. The results of this study show that d-AMPH and m-AMPH have similar behavioral effects, which previous studies had already reported. On the other hand, this study demonstrated that the m-AMPH induces oxidative damage greater than d-AMPH, showing neurochemical differences previously unknown.
Behavioural and histopathological assessment of the effects of periodic fasting on pentylenetetrazol-induced seizures in rats.
Nutritional neuroscience, 2013

Periodic fasting (PF) was suggested to display antiepileptic and neuroprotective effects, which is in stark contrast to severe fasting or starvation. However, these beneficial effects seem to depend on the type and duration of the used feeding protocol. There are discrepancies concerning both antiepileptic and neuroprotective effects of a PF-diet during repetitive seizures in different epilepsy models. This study was designed to evaluate the effects of different PF protocols on behavioural and histopathological consequences of epilepsy in adult rats.
Anxiolytic and antidepressant effects of intracerebroventricularly administered somatostatin: behavioral and neurophysiological evidence.
Neuroscience, 2008

Somatostatin (SST) is a cyclic polypeptide that inhibits the release of a variety of regulatory hormones (e.g. growth hormone, insulin, glucagon, thyrotropin). Moreover, SST is widely distributed within the CNS, acting both as a neurotransmitter and as a neuromodulator of other neurotransmitter systems. However, despite its extensive expression in limbic areas, and its co-localization with GABA, a neurotransmitter previously implicated in emotion, the effects of SST on anxiety and depression have not been investigated. By performing intraventricular infusions in rats we demonstrate, for the first time, that SST has anxiolytic- and antidepressant-like effects in the elevated plus-maze and forced swim test, respectively. In addition, by performing local field potential recordings of hippocampal theta activity evoked by reticular stimulation in urethane-anesthetized rats we also show that SST application suppresses the frequency of theta in a similar fashion to diazepam. This neurophysiological signature, common to all classes of anxiolytic drugs (i.e. benzodiazepines, selective 5-HT reuptake inhibitors, 5-HT1A agonists) provides strong converging evidence for the anxiolytic-like characteristics of SST. Our pharmacological antagonism experiments with bicuculline further suggest that the anxiolytic effect of SST may be attributable to the interaction of SST with GABA, whereas the antidepressant-like effect of SST may be GABA-independent. In addition to contributing to the current understanding of the role of neuropeptides in mood and emotion, these findings support a clinical role for SST (or its analogues) in the treatment of anxiety and depression.
Mild Contralesional Hypothermia Reduces Use of the Unimpaired Forelimb in a Skilled Reaching Task After Motor Cortex Injury in Rats.
Therapeutic hypothermia and temperature management, 2018

Therapeutic hypothermia (TH) mitigates neuronal injury in models of ischemic stroke. Although this therapy is meant for injured tissue, most protocols cool the whole body, including the contralesional hemisphere. Neuroplasticity responses within this hemisphere can affect functional outcome. Thus, cooling the contralesional hemisphere serves no clear neuroprotective function and may instead be detrimental. In this study, we cooled the contralesional hemisphere to determine whether this harms behavioral recovery after cortical injury in rats. All rats were trained on skilled reaching and walking tasks. Rats then received a motor cortex insult contralateral to their dominant paw after which they were randomly assigned to focal contralesional TH (∼33°C) for 1-48, 1-97, or 48-96 hours postinjury, or to a normothermic control group. Contralesional cooling did not impact lesion volume (p = 0.371) and had minimal impact on neurological outcome of the impaired limb. However, rats cooled early were significantly less likely to shift paw preference to the unimpaired paw (p ≤ 0.043), suggesting that cooling reduced learned nonuse. In a second experiment, we tested whether cooling impaired learning of the skilled reaching task in naive rats. Localized TH applied to the hemisphere contralateral or ipsilateral to the preferred paw did not impair learning (p ≥ 0.677) or dendritic branching/length in the motor cortex (p ≥ 0.105). In conclusion, localized TH did not impair learning or plasticity in the absence of neural injury, but contralesional TH may reduce unwanted shifts in limb preference after stroke.
Conditions and constraints for astrocyte calcium signaling in the hippocampal mossy fiber pathway.
Neuron, 2014

The spatiotemporal activities of astrocyte Ca²⁺ signaling in mature neuronal circuits remain unclear. We used genetically encoded Ca²⁺ and glutamate indicators as well as pharmacogenetic and electrical control of neurotransmitter release to explore astrocyte activity in the hippocampal mossy fiber pathway. Our data revealed numerous localized, spontaneous Ca²⁺ signals in astrocyte branches and territories, but these were not driven by neuronal activity or glutamate. Moreover, evoked astrocyte Ca²⁺ signaling changed linearly with the number of mossy fiber action potentials. Under these settings, astrocyte responses were global, suppressed by neurotransmitter clearance, and mediated by glutamate and GABA. Thus, astrocyte engagement in the fully developed mossy fiber pathway was slow and territorial, contrary to that frequently proposed for astrocytes within microcircuits. We show that astrocyte Ca²⁺ signaling functionally segregates large volumes of neuropil and that these transients are not suited for responding to, or regulating, single synapses in the mossy fiber pathway.
Improved Social Interaction, Recognition and Working Memory with Cannabidiol Treatment in a Prenatal Infection (poly I:C) Rat Model.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2017

Neuropsychiatric disorders such as schizophrenia are associated with cognitive impairment, including learning, memory and attention deficits. Antipsychotic drugs are limited in their efficacy to improve cognition; therefore, new therapeutic agents are required. Cannabidiol (CBD), the non-intoxicating component of cannabis, has anti-inflammatory, neuroprotective and antipsychotic-like properties; however, its ability to improve the cognitive deficits of schizophrenia remains unclear. Using a prenatal infection model, we examined the effect of chronic CBD treatment on cognition and social interaction. Time-mated pregnant Sprague-Dawley rats (n=16) were administered polyinosinic-polycytidilic acid (poly I:C) (POLY; 4 mg/kg) or saline (CONT) at gestation day 15. Male offspring (PN56) were injected twice daily with 10 mg/kg CBD (CONT+CBD, POLY+CBD; n=12 per group) or vehicle (VEH; CONT+VEH, POLY+VEH; n=12 per group) for 3 weeks. Body weight, food and water intake was measured weekly. The Novel Object Recognition and rewarded T-maze alternation tests assessed recognition and working memory, respectively, and the social interaction test assessed sociability. POLY+VEH offspring exhibited impaired recognition and working memory, and reduced social interaction compared to CONT+VEH offspring (p<0.01). CBD treatment significantly improved recognition, working memory and social interaction deficits in the poly I:C model (p<0.01 vs POLY+VEH), did not affect total body weight gain, food or water intake, and had no effect in control animals (all p>0.05). In conclusion, chronic CBD administration can attenuate the social interaction and cognitive deficits induced by prenatal poly I:C infection. These novel findings present interesting implications for potential use of CBD in treating the cognitive deficits and social withdrawal of schizophrenia.
End-to-end neural system identification with neural information flow.
PLoS computational biology, 2021

Neural information flow (NIF) provides a novel approach for system identification in neuroscience. It models the neural computations in multiple brain regions and can be trained end-to-end via stochastic gradient descent from noninvasive data. NIF models represent neural information processing via a network of coupled tensors, each encoding the representation of the sensory input contained in a brain region. The elements of these tensors can be interpreted as cortical columns whose activity encodes the presence of a specific feature in a spatiotemporal location. Each tensor is coupled to the measured data specific to a brain region via low-rank observation models that can be decomposed into the spatial, temporal and feature receptive fields of a localized neuronal population. Both these observation models and the convolutional weights defining the information processing within regions are learned end-to-end by predicting the neural signal during sensory stimulation. We trained a NIF model on the activity of early visual areas using a large-scale fMRI dataset recorded in a single participant. We show that we can recover plausible visual representations and population receptive fields that are consistent with empirical findings.
The social defeat/overcrowding murine psychosocial stress model results in a pharmacologically reversible body weight gain but not depression - related behaviours.
Neurobiology of stress, 2018

Depression is a highly prevalent psychiatric disorder, yet its etiology is not well understood. The validation of animal models is therefore a critical step towards advancing knowledge about the neurobiology of depression. Psychosocial stress has been promoted as a prospective animal model of depression, however, different protocols exist with variable responses, and further investigations are therefore required. We aimed to characterise the behavioural and body weight responses to the social defeat/overcrowding (SD/OC) model and to explore the effects of the antidepressant fluoxetine and the peroxynitrite scavenger, Cu
Improving BCI performance through co-adaptation: applications to the P300-speller.
Annals of physical and rehabilitation medicine, 2015

A well-known neurophysiological marker that can easily be captured with electroencephalography (EEG) is the so-called P300: a positive signal deflection occurring at about 300 ms after a relevant stimulus. This brain response is particularly salient when the target stimulus is rare among a series of distracting stimuli, whatever the type of sensory input. Therefore, it has been proposed and extensively studied as a possible feature for direct brain-computer communication. The most advanced non-invasive BCI application based on this principle is the P300-speller. However, it is still a matter of debate whether this application will prove relevant to any population of patients. In a series of recent theoretical and empirical studies, we have been using this P300-based paradigm to push forward the performance of non-invasive BCI. This paper summarizes the proposed improvements and obtained results. Importantly, those could be generalized to many kinds of BCI, beyond this particular application. Indeed, they relate to most of the key components of a closed-loop BCI, namely: improving the accuracy of the system by trying to detect and correct for errors automatically; optimizing the computer's speed-accuracy trade-off by endowing it with adaptive behavior; but also simplifying the hardware and time for set-up in the aim of routine use in patients. Our results emphasize the importance of the closed-loop interaction and of the ensuing co-adaptation between the user and the machine whenever possible. Most of our evaluations have been conducted in healthy subjects. We conclude with perspectives for clinical applications.
Neurogenic role of the depolarizing chloride gradient revealed by global overexpression of KCC2 from the onset of development.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2008

GABA- and glycine-induced depolarization is thought to provide important developmental signals, but the role of the underlying chloride gradient has not been examined from the onset of development. We therefore overexpressed globally the potassium-chloride cotransporter 2 (KCC2) in newly fertilized zebrafish embryos to reverse the chloride gradient. This rendered glycine hyperpolarizing in all neurons, tested at the time that motor behaviors (but not native KCC2) first appear. KCC2 overexpression resulted in fewer mature spontaneously active spinal neurons, more immature silent neurons, and disrupted motor activity. We observed fewer motoneurons and interneurons, a reduction in the elaboration of axonal tracts, and smaller brains and spinal cords. However, we observed no increased apoptosis and a normal complement of sensory neurons, glia, and progenitors. These results suggest that chloride-mediated excitation plays a crucial role in promoting neurogenesis from the earliest stages of embryonic development.
Serum Response Factor Promotes Dopaminergic Neuron Survival via Activation of Beclin 1-Dependent Autophagy.
Neuroscience, 2018

Serum response factor (SRF), a transcription factor highly expressed in neurons, is involved in neuronal survival and the pathogenesis of some neurodegenerative disorders. The ablation of SRF renders the midbrain dopaminergic (DA) neurons vulnerable to 1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine-induced neurotoxicity, however, the underlying mechanisms remain poorly understood. Here, we report decreased SRF levels in the substantia nigra (SN) of rotenone-treated rats that was associated with the loss of tyrosine hydroxylase (TH)-positive neurons. SRF expression was also reduced in rotenone-treated PC12 cells in vitro. In addition, Srf knockdown augmented rotenone-induced toxicity in PC12 cells. In contrast, overexpression of Srf attenuated the cells' sensitivity to rotenone and alleviated rotenone-induced α-synuclein accumulation. The protective effect of SRF was abolished when the expression of autophagy-related proteins Beclin 1 and Atg5 was suppressed. These results suggested that SRF may promote DA neuron survival by regulating autophagy, and thus serves as a critical molecule in PD progression.
Ethanol induces cytostasis of cortical basal progenitors.
Journal of biomedical science, 2016

Developing brain is a major target for alcohol's actions and neurological/functional abnormalities include microencephaly, reduced frontal cortex, mental retardation and attention-deficits. Previous studies have shown that ethanol altered the lateral ventricular neuroepithelial cell proliferation. However, the effect of ethanol on subventricular basal progenitors which generate majority of the cortical layers is not known.
IL-10 alters immunoproteostasis in APP mice, increasing plaque burden and worsening cognitive behavior.
Neuron, 2015

Anti-inflammatory strategies are proposed to have beneficial effects in Alzheimer's disease. To explore how anti-inflammatory cytokine signaling affects Aβ pathology, we investigated the effects of adeno-associated virus (AAV2/1)-mediated expression of Interleukin (IL)-10 in the brains of APP transgenic mouse models. IL-10 expression resulted in increased Aβ accumulation and impaired memory in APP mice. A focused transcriptome analysis revealed changes consistent with enhanced IL-10 signaling and increased ApoE expression in IL-10-expressing APP mice. ApoE protein was selectively increased in the plaque-associated insoluble cellular fraction, likely because of direct interaction with aggregated Aβ in the IL-10-expressing APP mice. Ex vivo studies also show that IL-10 and ApoE can individually impair glial Aβ phagocytosis. Our observations that IL-10 has an unexpected negative effect on Aβ proteostasis and cognition in APP mouse models demonstrate the complex interplay between innate immunity and proteostasis in neurodegenerative diseases, an interaction we call immunoproteostasis.
Modification of activation kinetics of delayed rectifier K+ currents and neuronal excitability by methyl-β-cyclodextrin.
Neuroscience, 2011

The effects of methyl-β-cyclodextrin (MβCD), an oligosaccharide, on ion currents were investigated in differentiated NG108-15 neuronal cells. In NG108-15 cells treated with dibutyryl cyclic AMP, the expression level of the K(V)3.1 mRNA was elevated. Depletion of membrane cholesterol by exposing cells to MβCD (1 mM) resulted in a significant reduction of the activation kinetics of delayed rectifier K(+) current (I(K)((DR))) in these cells. However, neither activation nor inactivation curve of I(K(DR)) was altered following MβCD treatment. In current-clamp recordings, in MβCD-treated cells, the instantaneous frequency of the firing in response to long-lasting current stimuli was reduced. In a modified Hodgkin-Huxley neuron, the upward shift in the relationship of activation/deactivation time constant of I(K(DR)) versus membrane potential causes a reduction of I(K(DR)) amplitude accompanied by an increase in the width of action potentials. In the studies from a high-frequency modeled neuron, reduction of voltage-dependent activation of I(K(DR)) can also facilitate spike-frequency adaptation. In a simulated network of spiking neurons, the increased activation/deactivation time constant of I(K(DR)) slowed repetitive firing. Taken together, MβCD may slow activation kinetics of I(K(DR)) and confer a trigger for the propensity to develop spike-frequency adaptation in neurons or neuroendocrine cells.