rudyvdbrink/CitationDatabase huggingface dataset:
Plasmodium berghei-induced malaria decreases pain sensitivity in mice.
The Onderstepoort journal of veterinary research, 2021

Various types of pain were reported by people with Plasmodium falciparum and were mostly attributed to a symptom of malarial infection. Neural processes of pain sensation during malarial infection and their contributions to malaria-related death are poorly understood. Thus, these form the focus of this study. Swiss mice used for this study were randomly divided into two groups. Animals in the first group (Pb-infected group) were inoculated with Plasmodium berghei to induce malaria whilst the other group (intact group) was not infected. Formalin test was used to assess pain sensitivity in both groups and using various antagonists, the possible mechanism for deviation in pain sensitivity was probed. Also, plasma and brain samples collected from animals in both groups were subjected to biochemical and/or histological studies. The results showed that Pb-infected mice exhibited diminished pain-related behaviours to noxious chemical. The observed parasite-induced analgesia appeared to be synergistically mediated via µ-opioid, α2 and 5HT2A receptors. When varied drugs capable of decreasing pain threshold (pro-nociceptive drugs) were used, the survival rate was not significantly different in the Pb-infected mice. This showed little or no contribution of the pain processing system to malaria-related death. Also, using an anti-CD68 antibody, there was no immunopositive cell in the brain to attribute the observed effects to cerebral malaria. Although in the haematoxylin and eosin-stained tissues, there were mild morphological changes in the motor and anterior cingulate cortices. In conclusion, the pain symptom was remarkably decreased in the animal model for malaria, and thus, the model may not be appropriate for investigating malaria-linked pain as reported in humans. This is the first report showing that at a critical point, the malaria parasite caused pain-relieving effects in Swiss mice.
Altered social cognition in male BDNF heterozygous mice and following chronic methamphetamine exposure.
Behavioural brain research, 2016

Growing clinical evidence suggests that persistent psychosis which occurs in methamphetamine users is closely related to schizophrenia. However, preclinical studies in animal models have focussed on psychosis-related behaviours following methamphetamine, and less work has been done to assess endophenotypes relevant to other deficits observed in schizophrenia. Altered social behaviour is a feature of both the negative symptoms and cognitive deficits in schizophrenia, and significantly impacts patient functioning. We recently found that brain-derived neurotrophic factor (BDNF) heterozygous mice show disrupted sensitization to methamphetamine, supporting other work suggesting an important role of this neurotrophin in the pathophysiology of psychosis and the neuronal response to stimulant drugs. In the current study, we assessed social and cognitive behaviours in methamphetamine-treated BDNF heterozygous mice and wildtype littermate controls. Following chronic methamphetamine exposure male wildtype mice showed a 50% reduction in social novelty preference. Vehicle-treated male BDNF heterozygous mice showed a similar impairment in social novelty preference, with a trend for no further disruption by methamphetamine exposure. Female mice were unaffected in this task, and no groups showed any changes in sociability or short-term spatial memory. These findings suggest that chronic methamphetamine alters behaviour relevant to disruption of social cognition in schizophrenia, supporting other studies which demonstrate a close resemblance between persistent methamphetamine psychosis and schizophrenia. Together these findings suggest that dynamic regulation of BDNF signalling is necessary to mediate the effects of methamphetamine on behaviours relevant to schizophrenia.
Phosphodiesterase-10A Inverse Changes in Striatopallidal and Striatoentopeduncular Pathways of a Transgenic Mouse Model of 
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2017

We report that changes of phosphodiesterase-10A (PDE10A) can map widespread functional imbalance of basal ganglia circuits in a mouse model of DYT1 dystonia overexpressing mutant torsinA. PDE10A is a key enzyme in the catabolism of second messenger cAMP and cGMP, whose synthesis is stimulated by D1 receptors and inhibited by D2 receptors preferentially expressed in striatoentopeducuncular/substantia nigra or striatopallidal pathways, respectively. PDE10A was studied in control mice (NT) and in mice carrying human wild-type torsinA (hWT) or mutant torsinA (hMT). Quantitative analysis of PDE10A expression was assessed in different brain areas by rabbit anti-PDE10A antibody immunohistochemistry and Western blotting. PDE10A-dependent cAMP hydrolyzing activity and PDE10A mRNA were also assessed. Striatopallidal neurons were identified by rabbit anti-enkephalin antibody.In NT mice, PDE10A is equally expressed in medium spiny striatal neurons and in their projections to entopeduncular nucleus/substantia nigra and to external globus pallidus. In hMT mice, PDE10A content selectively increases in enkephalin-positive striatal neuronal bodies; moreover, PDE10A expression and activity in hMT mice, compared with NT mice, significantly increase in globus pallidus but decrease in entopeduncular nucleus/substantia nigra. Similar changes of PDE10A occur in hWT mice, but such changes are not always significant. However, PDE10A mRNA expression appears comparable among NT, hWT, and hMT mice.In
Quantitative 3D Ultrastructure of Thalamocortical Synapses from the "Lemniscal" Ventral Posteromedial Nucleus in Mouse Barrel Cortex.
Cerebral cortex (New York, N.Y. : 1991), 2018

Thalamocortical synapses from "lemniscal" neurons of the dorsomedial portion of the rodent ventral posteromedial nucleus (VPMdm) are able to induce with remarkable efficacy, despite their relative low numbers, the firing of primary somatosensory cortex (S1) layer 4 (L4) neurons. To which extent this high efficacy depends on structural synaptic features remains unclear. Using both serial transmission (TEM) and focused ion beam milling scanning electron microscopy (FIB/SEM), we 3D-reconstructed and quantitatively analyzed anterogradely labeled VPMdm axons in L4 of adult mouse S1. All VPMdm synapses are asymmetric. Virtually all are established by axonal boutons, 53% of which contact multiple (2-4) elements (overall synapse/bouton ratio = 1.6). Most boutons are large (mean 0.47 μm3), and contain 1-3 mitochondria. Vesicle pools and postsynaptic density (PSD) surface areas are large compared to others in rodent cortex. Most PSDs are complex. Most synapses (83%) are established on dendritic spine heads. Furthermore, 15% of the postsynaptic spines receive a second, symmetric synapse. In addition, 13% of the spine heads have a large protrusion inserted into a membrane pouch of the VPMdm bouton. The unusual combination of structural features in VPMdm synapses is likely to contribute significantly to the high efficacy, strength, and plasticity of these thalamocortical synapses.
Effects of chemogenetic manipulation of the nucleus accumbens core in male C57BL/6J mice.
Alcohol (Fayetteville, N.Y.), 2021

Binge drinking is a widespread public health concern with limited effective treatment options. To better select pharmaceutical targets, it is imperative to expand our knowledge of the underlying neural mechanisms involved in binge drinking. Our previous experiments in C57BL/6J female mice found that increasing activity in the nucleus accumbens (NAc) core using excitatory Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) reduced binge-like drinking. These results differed from what has been found in males; however, it is unclear whether differences in experimental procedures or sex underlie these discrepancies. We matched the conditions used in our female study and asked whether bidirectional manipulation of NAc core activity has different effects on binge-like drinking in males. Male C57BL/6J mice were stereotaxically injected with AAV2 hSyn-HA hM3Dq (excitatory), -hM4Di (inhibitory), or -eGFP bilaterally into the NAc core. We tested the effects of altering NAc activity on binge-like ethanol intake using Drinking in the Dark (DID). During the first week, mice were pre-treated with vehicle to establish baseline ethanol intake. In week 2, mice were treated with 1 mg/kg CNO prior to DID to determine the effects of DREADD-induced changes in NAc core activity on ethanol intake. Decreasing activity via CNO/hM4Di significantly decreased binge-like drinking in male mice relative to eGFP and hM4Di groups. We also measured intake of sucrose, quinine, and water after CNO treatment and found that increasing NAc core activity via CNO/hM3Dq increased quinine intake, and increased water intake over time. We did not observe significant differences in the GFP or hM4Di groups. This work suggests there exist apparent sex-related differences in NAc core contributions to binge-like alcohol drinking, thus demonstrating the need for inclusion of both sexes in future work.
Epigenetic regulation in the pathophysiology of Lewy body dementia.
Progress in neurobiology, 2020

Lewy body dementia encompasses both dementia with Lewy bodies and Parkinson's disease dementia. Although both are common causes of dementia, they remain relatively understudied. The review summarises the clinico-pathologic characteristics of Lewy Body dementia and discusses the genetic and environmental evidence contributing to the risk of developing the condition. Considering that the pathophysiology of Lewy body dementia is not yet fully understood, here we focus on the role of epigenetic mechanisms as potential key mediators of gene-environment interactions in the development of the disease. We examine available important data on genomics, epigenomics, gene expression and proteomic studies in Lewy body dementia on human post-mortem brain and peripheral tissues. Genetic variation and epigenetic modifications in key genes involved in the disorder, such as apolipoprotein E (APOE), α-synuclein (SNCA) and glucocerobrosidase (GBA), suggest a central involvement of epigenetics in DLB but conclusive evidence is scarce. This is due to limitations of existing literature, such as small sample sizes, lack of replication and lack of studies interrogating cell-type specific epigenetic modifications in the brain. Future research in the field can improve the understanding of this common but complex and rapidly progressing type of dementia and potentially open early diagnostic and effective therapeutic targets.
Trauma and mental health in South Africa: Overview.
Psychological trauma : theory, research, practice and policy, 2017

Provides an introduction to this special edition of Psychological Trauma. The papers included in this special section focus on aspects of trauma and the effects of trauma in a cultural context that pertains to the way of life in South Africa. These articles highlight the complexities of the effects of trauma and call for tailored interventions to address the lasting effects on health and mental health. (PsycINFO Database Record
Holistic processing is not correlated with face-identification accuracy.
Psychological science, 2010

The current study tested the widespread assumption that holistic processing is important for the identification of upright faces. In two experiments, we show that (a) there are large individual differences in the magnitude of the composite face effect and face-identification accuracy and (b) the correlation between the magnitude of the composite face effect and face-identification accuracy is essentially zero. These findings are inconsistent with the claim that holistic processing, as indexed by the composite face effect, significantly influences accuracy in a face-identification task.
D-2-Hydroxyglutarate Is Necessary and Sufficient for Isocitrate Dehydrogenase 1 Mutant-Induced 
Molecular cancer research : MCR, 2018

Mutant isocitrate dehydrogenase (IDH) 1/2 converts α-ketoglutarate (α-KG) to D-2 hydroxyglutarate (D-2-HG), a putative oncometabolite that can inhibit α-KG-dependent enzymes, including ten-eleven translocation methylcytosine dioxygenase (TET) DNA demethylases. We recently established that miRNAs are components of the IDH1 mutant-associated glioma CpG island methylator phenotype (G-CIMP) and specifically identified MIR148A as a tumor-suppressive miRNA within G-CIMP. However, the precise mechanism by which mutant IDH induces hypermethylation of
PINK1 phosphorylates Drp1
EMBO reports, 2020

Impairment of PINK1/parkin-mediated mitophagy is currently proposed to be the molecular basis of mitochondrial abnormality in Parkinson's disease (PD). We here demonstrate that PINK1 directly phosphorylates Drp1 on S616. Drp1
Maternal reproductive performance and fetal development of the Wistar Audiogenic Rat (WAR) strain.
Systems biology in reproductive medicine, 2019

Wistar Audiogenic Rat (WAR) strain is an animal model for epilepsy studies, the chronic multifactorial disease that affects millions of people worldwide. The animals of this strain are genetically predisposed to sound-induced seizures, called audiogenic seizures, and have been used for many years in studies to understand the mechanisms involved in the epilepsies and their neuropsychiatric comorbidities, as well as the screening of potential anti-convulsant agents. Nevertheless, little is known about the reproductive characteristics of these animals. The main goal of this study was to characterize the female reproductive performance and the fetal growth of WARs in comparison to the Wistar rats, obtaining important information for physiology and behavioral studies, as well as for the preservation of the strain. The results indicated few differences between WAR and Wistar regarding the female reproductive performance. There was no significant difference in the number of pregnant females by mating, number of live births per female, number of cells per blastocyst, and several characteristics related to reproductive performance, such as pre- and post-implantation losses. However, significant differences were observed in birth weight and weight gain until weaning, with WAR animals presenting a body weight below Wistar at birth and reduced body weight gain during the lactation period. In addition, the WAR females showed lower body weight on the day 20 of pregnancy and a larger number of corpora lutea, when compared with those of Wistar animals. Thus, we conclude that although Wistar and WAR strains have few differences in their reproductive performance, which might impact future physiological life challenges or others experimentally induced procedures, it still is a very viable strain regarding reproduction. Abbreviations: CONCEA: National Council for the Control of Animal Experimentation; GEPR: genetically epilepsy-prone rats; WAR: Wistar Audiogenic Rat.
Topiramate-induced intractable cough during migraine prophylaxis.
Headache, 2010

Topiramate is a highly effective drug in migraine prophylaxis and is considered a first-line treatment. The evidence for the efficacy of topiramate is based upon the results of several large, randomized, double-blind, placebo-controlled trials. Adverse events (AEs) are common and require discontinuation of the treatment in about 20-25% of patients, but they are rarely severe. There are reviews regarding topiramate-related AEs representing a large number of patients treated in controlled trials. The most common AEs are weight loss, dizziness, somnolence, abnormal thinking, fatigue, ataxia, confusion, paresthesias, impaired concentration, nervousness, amnesia, and language difficulties. The development of cough has never been reported as an AE during topiramate prophylaxis for migraine. We present 3 cases in which the prophylactic treatment for migraine with topiramate was discontinued due to the onset of primary intractable coughing.
A brief period of moderate noxious stimulation induces hemorrhage and impairs locomotor recovery after spinal cord injury.
Physiology & behavior, 2019

Spinal cord injury (SCI) is often accompanied by additional tissue damage (polytrauma) that provides a source of pain input. Our studies suggest that this pain input may be detrimental to long-term recovery. In a rodent model, we have shown that engaging pain (nociceptive) fibers caudal to a lower thoracic contusion SCI impairs recovery of locomotor function and increases tissue loss (secondary injury) and hemorrhage at the site of injury. In these studies, nociceptive fibers were activated using intermittent electrical stimulation. The stimulation parameters were derived from earlier studies demonstrating that 6 min of noxious stimulation, at an intensity (1.5 mA) that engages unmyelinated C (pain) fibers, induces a form of maladaptive plasticity within the lumbosacral spinal cord. We hypothesized that both shorter bouts of nociceptive input and lower intensities of stimulation will decrease locomotor function and increase spinal cord hemorrhage when rats have a spinal cord contusion. To test this, the present study exposed rats to electrical stimulation 24 h after a moderate lower thoracic contusion SCI. One group of rats received 1.5 mA stimulation for 0, 14.4, 72, or 180 s. Another group received six minutes of stimulation at 0, 0.17, 0.5, and 1.5 mA. Just 72 s of stimulation induced an acute disruption in motor performance, increased hemorrhage, and undermined the recovery of locomotor function. Likewise, less intense (0.5 mA) stimulation produced an acute disruption in motor performance, fueled hemorrhage, and impaired long-term recovery. The results imply that a brief period of moderate pain input can trigger hemorrhage after SCI and undermine long-term recovery. This highlights the importance of managing nociceptive signals after concurrent peripheral and central nervous system injuries.
Reassessing optimal neural population codes with neurometric functions.
Proceedings of the National Academy of Sciences of the United States of America, 2011

Cortical circuits perform the computations underlying rapid perceptual decisions within a few dozen milliseconds with each neuron emitting only a few spikes. Under these conditions, the theoretical analysis of neural population codes is challenging, as the most commonly used theoretical tool--Fisher information--can lead to erroneous conclusions about the optimality of different coding schemes. Here we revisit the effect of tuning function width and correlation structure on neural population codes based on ideal observer analysis in both a discrimination and a reconstruction task. We show that the optimal tuning function width and the optimal correlation structure in both paradigms strongly depend on the available decoding time in a very similar way. In contrast, population codes optimized for Fisher information do not depend on decoding time and are severely suboptimal when only few spikes are available. In addition, we use the neurometric functions of the ideal observer in the classification task to investigate the differential coding properties of these Fisher-optimal codes for fine and coarse discrimination. We find that the discrimination error for these codes does not decrease to zero with increasing population size, even in simple coarse discrimination tasks. Our results suggest that quite different population codes may be optimal for rapid decoding in cortical computations than those inferred from the optimization of Fisher information.
Suppression of HIV-1 transcriptional elongation by a DING phosphatase.
Journal of cellular biochemistry, 2011

HIV-1 gene transcription is controlled by the cooperation of viral and host factors which bind to specific DNA sequences within the viral promoter spanning the long terminal repeat (LTR). Previously we showed that the St. John's Wort DING phosphatase, p27SJ, suppresses HIV-1 gene transcription by binding to the viral protein Tat and preventing its nuclear import. Here, we describe the inhibitory effect of p27SJ on the phosphorylation of the C-terminal domain (CTD) of RNA polymerase II (RNAPII). This inhibition leads to the suppression of the association of RNAPII with the LTR. Inhibition of binding of RNAPII to LTR by p27SJ resulted in the suppression of LTR transcription elongation and a decrease in LTR transcriptional activity. Another form of the St. John's Wort DING phosphatase, p38SJ, also suppressed binding of RNAPII to the LTR, reduced transcription elongation and was even more powerful than p27SJ in inhibiting the transcriptional activity of the LTR. Our data suggest a possible mechanism by which the p27SJ/p38SJ DING phosphatase can regulate HIV-1 LTR expression by inhibiting phosphorylation of the CTD of RNAPII and suppressing LTR transcription elongation.
Risk factors for the onset and progression of Huntington disease.
Neurotoxicology, 2017

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder characterized by chorea, behavioural and psychiatric manifestations, and dementia, caused by a CAG triplet repeat expansion in the huntingtin gene. Systematic review of the literature was conducted to determine the risk factors for the onset and progression of HD. Multiple databases were searched, using terms specific to Huntington disease and to studies of aetiology, risk, prevention and genetics, limited to studies on human subjects published in English or French between 1950 and 2010. Two reviewers independently screened the abstracts and identified potentially relevant articles for full-text review using predetermined inclusion criteria. Three major categories of risk factors for onset of HD were identified: CAG repeat length in the huntingtin gene, CAG instability, and genetic modifiers. Of these, CAG repeat length in the huntingtin gene is the most important risk factor. For the progression of HD: genetic, demographic, past medical/clinical and environmental risk factors have been studied. Of these factors, genetic factors appear to play the most important role in the progression of HD. Among the potential risk factors, CAG repeat length in the mutant allele was found to be a relatively consistent and significant risk factor for the progression of HD, especially in motor, cognitive, and other neurological symptom deterioration. In addition, there were many consistent results in the literature indicating that a higher number of CAG repeats was associated with shorter survival, faster institutionalization, and earlier percutaneous endoscopic gastrostomy.
National epilepsy surgery support activity.
Annals of Indian Academy of Neurology, 2014

While there are over one million people with drug-resistant epilepsy in India, today, there are only a handful of centers equipped to undertake presurgical evaluation and epilepsy surgery. The only solution to overcome this large surgical treatment gap is to establish comprehensive epilepsy care centers across the country that are capable of evaluating and selecting the patients for epilepsy surgery with the locally available technology and in a cost-effective manner. The National Epilepsy Surgery Support Activity (NESSA) aims to provide proper guidance and support in establishing epilepsy surgery programs across India and in neighboring resource-poor countries, and in sustaining them.