rudyvdbrink/CitationDatabase huggingface dataset:
mGluR1 and mGluR5 Synergistically Control Cholinergic Synaptic Transmission in the Thalamic Reticular Nucleus.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2016

Acetylcholine (ACh) signaling is involved in a wide range of processes, including arousal, attention, and learning. An increasing number of studies indicate that cholinergic control of these functions is highly deterministic, mediated by synaptic afferents that generate reliable and precise responses in postsynaptic neurons. However, mechanisms that govern plastic changes of cholinergic synaptic strength are poorly understood, even though they are likely critical in shaping the impact of cholinergic inputs on neuronal networks. We have recently shown that in the thalamic reticular nucleus (TRN), synaptic release of ACh generates excitatory-inhibitory biphasic postsynaptic responses, mediated by the activation of α4β2 nicotinic (nAChRs) and M2 muscarinic receptors (mAChRs), respectively. Here, using voltage-clamp recordings from TRN neurons in thalamocortical slices of mice, we demonstrate that the activation of Group I metabotropic glutamate receptors (mGluRs) by ambient or synaptically released glutamate evokes transient increases of nicotinic EPSCs. Additionally, we find that the selective Group I mGluR agonist DHPG [(S)-3,5-dihydroxyphenylglycine] evokes long-term potentiation of nicotinic EPSCs (mGluR-nLTP), dependent on increases in postsynaptic Ca(2+) concentration and the activation of phospholipase C. Both the induction and the maintenance of mGluR-nLTP require synergistic activation of mGluR1 and mGluR5. Together, our results show that postsynaptic Group I mGluRs are critically involved in the regulation of cholinergic synaptic strength on different time scales, suggesting that cholinergic control of local thalamic circuits is highly context-dependent and regulated by the overall levels of glutamatergic afferent activity.
Analysis of motor function in 6-month-old male and female 3xTg-AD mice.
Behavioural brain research, 2015

The 3xTg-AD mouse has high validity as a model of Alzheimer's disease (AD) because it develops both amyloid beta plaques and neurofibrillary tangles. Human patients with AD typically develop motor deficits, which worsen as the disease progresses, but 3xTg-AD mice have been reported to show enhanced motor abilities. We investigated the motor behaviour phenotype of male and female 3xTg-AD and B6129SF2 wildtype mice on a battery of motor behaviours at 6 months of age. Compared to wildtype mice, the 3xTg-AD mice had enhanced motor performance on the Rotarod, but worse performance on the grid suspension task. In gait analysis 3xTg-AD mice had a longer stride length and made more foot slips on the balance beam than wildtype mice. There was no overall difference in voluntary wheel-running activity between genotypes, but there was a disruption in circadian activity rhythm in 3xTg-AD mice. In some motor tasks, such as the Rotarod and balance beam, females appeared to perform better than males, but this sex differences was accounted for by differences in body weight. Our results indicate that while the 3xTg-AD mice show enhanced performance on the Rotarod, they have poorer performance on other motor behaviour tasks, indicating that their motor behaviour phenotype is more complex than previously reported. The presence of the P301L transgene may explain the enhancement of Rotarod performance but the poorer performance on other motor behaviour tasks may be due to other transgenes.
Contributions of central and systemic inflammation to the pathophysiology of Parkinson's disease.
Neuropharmacology, 2012

Idiopathic Parkinson's disease (PD) represents a complex interaction between the inherent vulnerability of the nigrostriatal dopaminergic system, a possible genetic predisposition, and exposure to environmental toxins including inflammatory triggers. Evidence now suggests that chronic neuroinflammation is consistently associated with the pathophysiology of PD. Activation of microglia and increased levels of pro-inflammatory mediators such as TNF-α, IL-1β and IL-6, reactive oxygen species and eicosanoids has been reported after post-mortem analysis of the substantia nigra from PD patients and in animal models of PD. It is hypothesised that chronically activated microglia secrete high levels of pro-inflammatory mediators which damage neurons and further activate microglia, resulting in a feed forward cycle promoting further inflammation and neurodegeneration. Moreover, nigrostriatal dopaminergic neurons are more vulnerable to pro-inflammatory and oxidative mediators than other cell types because of their low intracellular glutathione concentration. Systemic inflammation has also been suggested to contribute to neurodegeneration in PD, as lymphocyte infiltration has been observed in brains of PD patients and in animal models of PD, substantiating the current theory of a fundamental role of inflammation in neurodegeneration. We will examine the current evidence in the literature which offers insight into the premise that both central and systemic inflammation may contribute to neurodegeneration in PD. We will discuss the emerging possibility of the use of diagnostic tools such as imaging technologies for PD patients. Finally, we will present the immunomodulatory therapeutic strategies that are now under investigation and in clinical trials as potential neuroprotective drugs for PD.
Mitochondrial Biogenesis and Proteome Remodeling Promote One-Carbon Metabolism for T Cell Activation.
Cell metabolism, 2016

Naive T cell stimulation activates anabolic metabolism to fuel the transition from quiescence to growth and proliferation. Here we show that naive CD4(+) T cell activation induces a unique program of mitochondrial biogenesis and remodeling. Using mass spectrometry, we quantified protein dynamics during T cell activation. We identified substantial remodeling of the mitochondrial proteome over the first 24 hr of T cell activation to generate mitochondria with a distinct metabolic signature, with one-carbon metabolism as the most induced pathway. Salvage pathways and mitochondrial one-carbon metabolism, fed by serine, contribute to purine and thymidine synthesis to enable T cell proliferation and survival. Genetic inhibition of the mitochondrial serine catabolic enzyme SHMT2 impaired T cell survival in culture and antigen-specific T cell abundance in vivo. Thus, during T cell activation, mitochondrial proteome remodeling generates specialized mitochondria with enhanced one-carbon metabolism that is critical for T cell activation and survival.
Recalling and forgetting dreams: theta and alpha oscillations during sleep predict subsequent dream recall.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2011

Under the assumption that dream recall is a peculiar form of declarative memory, we have hypothesized that (1) the encoding of dream contents during sleep should share some electrophysiological mechanisms with the encoding of episodic memories of the awake brain and (2) recalling a dream(s) after awakening from non-rapid eye movement (NREM) and rapid eye movement (REM) sleep should be associated with different brain oscillations. Here, we report that cortical brain oscillations of human sleep are predictive of successful dream recall. In particular, after morning awakening from REM sleep, a higher frontal 5-7 Hz (theta) activity was associated with successful dream recall. This finding mirrors the increase in frontal theta activity during successful encoding of episodic memories in wakefulness. Moreover, in keeping with the different EEG background, a different predictive relationship was found after awakening from stage 2 NREM sleep. Specifically, a lower 8-12 Hz (alpha) oscillatory activity of the right temporal area was associated with a successful dream recall. These findings provide the first evidence of univocal cortical electroencephalographic correlates of dream recall, suggesting that the neurophysiological mechanisms underlying the encoding and recall of episodic memories may remain the same across different states of consciousness.
Novel potential pyrazolopyrimidine based translocator protein ligands for the evaluation of neuroinflammation with PET.
European journal of medicinal chemistry, 2018

Translocator protein (TSPO) is an interesting biological target because TSPO overexpression is associated with microglial activation caused by neuronal damage or neuroinflammation, and these activated microglia are involved in several central nervous system diseases. Herein, novel fluorinated ligands (14a-c and 16a-c) based on a 2-phenylpyrazolo[1,5-a]pyrimidin-3-yl acetamide scaffold were synthesized, and in vitro characterization of each of the novel ligands was performed to elucidate structure activity relationships. All of the newly synthesized ligands displayed nano-molar affinity for TSPO. Particularly, an in vitro affinity study suggests that 2-(5,7-diethyl-2-(4-(3-fluoro-2-methylpropoxy)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)-N,N-diethylacetamide (14a), which exhibited high nano-molar affinity for TSPO and proper lipophilicity, was suitable for in vivo brain studies. Thus, radiosynthesis from tosylate precursor 13a using fluorine-18 was performed, and [
Electrical and synaptic integration of glioma into neural circuits.
Nature, 2019

High-grade gliomas are lethal brain cancers whose progression is robustly regulated by neuronal activity. Activity-regulated release of growth factors promotes glioma growth, but this alone is insufficient to explain the effect that neuronal activity exerts on glioma progression. Here we show that neuron and glioma interactions include electrochemical communication through bona fide AMPA receptor-dependent neuron-glioma synapses. Neuronal activity also evokes non-synaptic activity-dependent potassium currents that are amplified by gap junction-mediated tumour interconnections, forming an electrically coupled network. Depolarization of glioma membranes assessed by in vivo optogenetics promotes proliferation, whereas pharmacologically or genetically blocking electrochemical signalling inhibits the growth of glioma xenografts and extends mouse survival. Emphasizing the positive feedback mechanisms by which gliomas increase neuronal excitability and thus activity-regulated glioma growth, human intraoperative electrocorticography demonstrates increased cortical excitability in the glioma-infiltrated brain. Together, these findings indicate that synaptic and electrical integration into neural circuits promotes glioma progression.
The columnar and laminar organization of inhibitory connections to neocortical excitatory cells.
Nature neuroscience, 2011

The cytoarchitectonic similarities of different neocortical regions have given rise to the idea of 'canonical' connectivity between excitatory neurons of different layers within a column. It is unclear whether similarly general organizational principles also exist for inhibitory neocortical circuits. Here we delineate and compare local inhibitory-to-excitatory wiring patterns in all principal layers of primary motor (M1), somatosensory (S1) and visual (V1) cortex, using genetically targeted photostimulation in a mouse knock-in line that conditionally expresses channelrhodopsin-2 in GABAergic neurons. Inhibitory inputs to excitatory neurons derived largely from the same cortical layer within a three-column diameter. However, subsets of pyramidal cells in layers 2/3 and 5B received extensive translaminar inhibition. These neurons were prominent in V1, where they might correspond to complex cells, less numerous in barrel cortex and absent in M1. Although inhibitory connection patterns were stereotypical, the abundance of individual motifs varied between regions and cells, potentially reflecting functional specializations.
Interactional synchrony: signals, mechanisms and benefits.
Social cognitive and affective neuroscience, 2021

Many group-living animals, humans included, occasionally synchronize their behavior with that of conspecifics. Social psychology and neuroscience have attempted to explain this phenomenon. Here we sought to integrate results around three themes: the stimuli, the mechanisms and the benefits of interactional synchrony. As regards stimuli, we asked what characteristics, apart from temporal regularity, prompt synchronization and found that stimulus modality and complexity are important. The high temporal resolution of the auditory system and the relevance of socio-emotional information endow auditory, multimodal, emotional and somewhat variable and adaptive sequences with particular synchronizing power. Looking at the mechanisms revealed that traditional perspectives emphasizing beat-based representations of others' signals conflict with more recent work investigating the perception of temporal regularity. Timing processes supported by striato-cortical loops represent any kind of repetitive interval sequence fairly automatically. Additionally, socio-emotional processes supported by posterior superior temporal cortex help endow such sequences with value motivating the extent of synchronizing. Synchronizing benefits arise from an increased predictability of incoming signals and include many positive outcomes ranging from basic information processing at the individual level to the bonding of dyads and larger groups.
Immune and viral therapies for malignant primary brain tumors.
Expert opinion on biological therapy, 2017

Glioblastoma multiforme (GBM) is a primary brain tumor with great lethality. Current standard of care with surgery, radiation therapy, and chemotherapy are ineffective in curing this disease. Recent advancements in biological therapies show promise in treating brain tumors. Areas covered: This article provides a review of: the peripheral activation of antigen presenting cells such as dendritic cells to stimulate T cells to recognize and destroy tumor cells within the brain; the ex vivo expansion and transfer of dendritic cells, T cells, and engineered T cells expressing chimeric antigen receptors to target cells bearing specific tumor antigens as well as monoclonal antibodies as immune check point inhibitors. Gene therapy approaches have also been utilized to employ viral vectors in transducing cells to express cytokines for activating immune responses to brain tumors. Finally, the article reviews engineering of viruses for oncolytic targeting and destruction of malignant tumors within the brain. Expert opinion: The ultimate goal of immune and viral approaches for treating malignant brain tumors is to cure this disease. Preclinical and clinical studies utilizing these biological therapeutic approaches for treating brain tumors have the potential to augment the current standard of care to provide potential curative therapies.
Global stroke statistics.
International journal of stroke : official journal of the International Stroke Society, 2014

In many countries, stroke is a lower priority than other diseases despite its public health impact. One issue is a lack of readily accessible comparative data to help make the case for the development of national stroke strategies. To assist in this process, we need to have a common repository of the latest published information on the impact of stroke worldwide. We aim to provide a repository of the most current incidence and mortality data on stroke available by country and illustrate the gaps in these data. We plan to update this repository annually and expand the scope to address other aspects of the burden of stroke. Data were compiled using two approaches: (1) an extensive literature review with a major focus on published systematic reviews on stroke incidence (between 1980 and May 14, 2013); and (2) direct acquisition and collation of data from the World Health Organization to present the most current estimates of stroke mortality for each country recognized by the World Health Organization. For mortality, ICD8, ICD9, and ICD10 mortality codes were extracted. Using population denominators crude stroke mortality was calculated, as well as adjusting for the World Health Organization world population. We used only the most recent year reported to the World Health Organization. Incidence rates for stroke were available for 52 countries, with some countries having incidence studies undertaken in more than one region. When adjusted to the World Health Organization world standard population, incidence rates for stroke ranged from 41 per 100 000 population per year in Nigeria (1971-74) to 316/ 100 000/year in urban Dar-es-Salaam (Tanzania). Some regions had three to fivefold greater incidence than other countries. Of the 123 countries reporting mortality data, crude mortality was greatest in Kazhakstan (in 2003). In many regions data were very old or nonexistent. Such country-level data are important for citizens, clinicians, and policy makers so that local and global strategies to reduce the overall burden of stroke can be implemented. Through this first annual review of country-specific stroke epidemiology, we hope to promote discussion and provide insights into the worldwide burden of stroke.
Post-error slowing is influenced by cognitive control demand.
Acta psychologica, 2014

Post-error slowing (PES) has been shown to reflect a control failure due to automatic attentional capture by the error. Here we aimed to assess whether PES also involves an increase in cognitive control. Using a cued-task-switching paradigm (Experiment 1) and a Stroop task (Experiment 2), the demand for top down control was manipulated. In Experiment 1, one group received dimension cues indicating the relevant stimulus dimension (e.g., "number") without specifying the response-category-to-key mapping, hence requiring considerable top down control. Another group was shown mapping cues providing information regarding both the relevant task identity and its category-to-key mapping (e.g., "one three"), requiring less top down control, and the last group received both types of cues, intermixed. In Experiment 2, one group performed a pure incongruent Stroop condition (name ink color of incongruent color names, high control demand), and another group received a pure neutral Stroop condition (name color patches, low control demand). In Experiment 2a, participants received the two conditions, intermixed. A larger PES was observed with dimension cues as compared with mapping cues, and with incongruent Stroop stimuli as compared to neutral stimuli, but not when the conditions were intermixed. These findings reveal that PES is influenced by the control demands that characterize the given block-wide experimental context and show that proactive cognitive control is involved in PES.
Anomalous vascularization in a Wnt medulloblastoma: a case report.
BMC neurology, 2016

Medulloblastoma is the most common malignant brain tumor in children. To date only few cases of medulloblastoma with hemorrhages have been reported in the literature. Although some studies speculate on the pathogenesis of this anomalous increased vascularization in medulloblastoma, the specific mechanism is still far from clearly understood. A correlation between molecular medulloblastoma subgroups and hemorrhagic features has not been reported, although recent preliminary studies described that WNT-subtype tumors display increased vascularization and hemorrhaging.
Epigenetic regulation of learning and memory by Drosophila EHMT/G9a.
PLoS biology, 2011

The epigenetic modification of chromatin structure and its effect on complex neuronal processes like learning and memory is an emerging field in neuroscience. However, little is known about the "writers" of the neuronal epigenome and how they lay down the basis for proper cognition. Here, we have dissected the neuronal function of the Drosophila euchromatin histone methyltransferase (EHMT), a member of a conserved protein family that methylates histone 3 at lysine 9 (H3K9). EHMT is widely expressed in the nervous system and other tissues, yet EHMT mutant flies are viable. Neurodevelopmental and behavioral analyses identified EHMT as a regulator of peripheral dendrite development, larval locomotor behavior, non-associative learning, and courtship memory. The requirement for EHMT in memory was mapped to 7B-Gal4 positive cells, which are, in adult brains, predominantly mushroom body neurons. Moreover, memory was restored by EHMT re-expression during adulthood, indicating that cognitive defects are reversible in EHMT mutants. To uncover the underlying molecular mechanisms, we generated genome-wide H3K9 dimethylation profiles by ChIP-seq. Loss of H3K9 dimethylation in EHMT mutants occurs at 5% of the euchromatic genome and is enriched at the 5' and 3' ends of distinct classes of genes that control neuronal and behavioral processes that are corrupted in EHMT mutants. Our study identifies Drosophila EHMT as a key regulator of cognition that orchestrates an epigenetic program featuring classic learning and memory genes. Our findings are relevant to the pathophysiological mechanisms underlying Kleefstra Syndrome, a severe form of intellectual disability caused by mutations in human EHMT1, and have potential therapeutic implications. Our work thus provides novel insights into the epigenetic control of cognition in health and disease.
An empirical explanation of the speed-distance effect.
PloS one, 2009

Understanding motion perception continues to be the subject of much debate, a central challenge being to account for why the speeds and directions seen accord with neither the physical movements of objects nor their projected movements on the retina. Here we investigate the varied perceptions of speed that occur when stimuli moving across the retina traverse different projected distances (the speed-distance effect). By analyzing a database of moving objects projected onto an image plane we show that this phenomenology can be quantitatively accounted for by the frequency of occurrence of image speeds generated by perspective transformation. These results indicate that speed-distance effects are determined empirically from accumulated past experience with the relationship between image speeds and moving objects.
Suicide risk in adolescents with fetal alcohol spectrum disorders.
Birth defects research, 2019

The teratogenic effects of prenatal alcohol exposure (PAE) have been extensively documented over the course of 45 years of research and psychiatric problems are pervasive in this population. In adults with PAE, suicidal risk is high but less is known about the suicidal risk in adolescents with fetal alcohol spectrum disorders (FASD). This study describes the prevalence of suicidal ideation and serious suicide attempts in a sample of 54 adolescents between the ages of 13 and 18 years with FASD.
Narratives of effort among Chinese, Hungarian and Chinese immigrant students in Hungary.
International journal of psychology : Journal international de psychologie, 2019

The present study aimed to reveal the effect of migration processes on the conceptualisation of effort involving two cultures with different approaches towards effort: China with an effort-promoting mindset and Hungary with an effort-repressing mindset. In the study, narrative approach was used in cross-sectional design involving Chinese, Hungarian and Chinese immigrant students living in Hungary. Altogether 139 students-49 Hungarian, 47 Chinese, 43 Chinese immigrants-aged 13-15 years provided narratives on past personal effort. Content analyses were done on 222 narratives. The results showed that the Chinese narratives of effort were characterised by learning and achievement orientation with elaborated effort process. In contrast, the Hungarian narratives were characterised by relationship orientation and emotional coping with a non-elaborated effort process. The narratives of the Chinese immigrants showed great similarity to those of the Chinese students reflecting academic effort, achievement goals and elaborated process. The findings suggest that the traditional Chinese approach towards effort persists in cultural transition, and academic effort tends to be a primary resource for educational success for the Chinese immigrant students in Hungary.