rudyvdbrink/CitationDatabase huggingface dataset:
Spatially displaced excitation contributes to the encoding of interrupted motion by a retinal direction-selective circuit.
eLife, 2021

Spatially distributed excitation and inhibition collectively shape a visual neuron's receptive field (RF) properties. In the direction-selective circuit of the mammalian retina, the role of strong null-direction inhibition of On-Off direction-selective ganglion cells (On-Off DSGCs) on their direction selectivity is well-studied. However, how excitatory inputs influence the On-Off DSGC's visual response is underexplored. Here, we report that On-Off DSGCs have a spatially displaced glutamatergic receptive field along their horizontal preferred-null motion axes. This displaced receptive field contributes to DSGC null-direction spiking during interrupted motion trajectories. Theoretical analyses indicate that population responses during interrupted motion may help populations of On-Off DSGCs signal the spatial location of moving objects in complex, naturalistic visual environments. Our study highlights that the direction-selective circuit exploits separate sets of mechanisms under different stimulus conditions, and these mechanisms may help encode multiple visual features.
Long-term outcome of endovascular therapy for acute basilar artery occlusion.
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 2021

The long-term functional outcome of acute basilar artery occlusion (BAO) patients who received modern endovascular therapy (EVT) is unclear. We sought to assess the long-term functional outcome of BAO patients treated with EVT and determine the prognostic factors associated with favorable outcome. We enrolled consecutive BAO patients who received EVT between December 2012 and December 2018 in this observational study. Baseline characteristics and outcomes were presented. Multivariable logistic regression analysis was performed to identify the prognostic factors associated with long-term outcome. Among the 177 BAO patients included in this study, 80 patients (45.2%) obtained favorable outcome and 97 patients (54.8%) had unfavorable outcome at long-term follow-up with a median observation time of 12 months (interquartile range, 3-19). A total of 67 patients (37.9%) died. National Institutes of Health Stroke Scale (NIHSS), posterior circulation Alberta Stroke Program Early Computed Tomography Score (pc-ASPECTS), time from stroke onset to recanalization, and recanalization condition were identified as independent predictors for long-term outcome. Over 40% of BAO patients who were treated with modern EVT achieved favorable outcome at long-term follow-up. NIHSS, pc-ASPECTS, time from stroke onset to recanalization, and recanalization condition were identified as independent prognostic factors of long-term outcome.
GSK3 signalling in neural development.
Nature reviews. Neuroscience, 2010

Recent evidence suggests that glycogen synthase kinase 3 (GSK3) proteins and their upstream and downstream regulators have key roles in many fundamental processes during neurodevelopment. Disruption of GSK3 signalling adversely affects brain development and is associated with several neurodevelopmental disorders. Here, we discuss the mechanisms by which GSK3 activity is regulated in the nervous system and provide an overview of the recent advances in the understanding of how GSK3 signalling controls neurogenesis, neuronal polarization and axon growth during brain development. These recent advances suggest that GSK3 is a crucial node that mediates various cellular processes that are controlled by multiple signalling molecules--for example, disrupted in schizophrenia 1 (DISC1), partitioning defective homologue 3 (PAR3), PAR6 and Wnt proteins--that regulate neurodevelopment.
Treadmill Exercise Attenuates L-DOPA-Induced Dyskinesia and Increases Striatal Levels of Glial Cell-Derived Neurotrophic Factor (GDNF) in Hemiparkinsonian Mice.
Molecular neurobiology, 2019

Exercise can act as a disease-modifying agent in Parkinson's disease (PD), and we have previously demonstrated that voluntary exercise in running wheels during 2 weeks normalizes striatopallidal dopaminergic signaling and prevents the development of L-DOPA-induced dyskinesia (LID) in C57BL/6 mice. We now tested whether LID in Swiss albino mice could be attenuated by treadmill-controlled exercise alone or in combination with the reference antidyskinetic drug amantadine. The daily intraperitoneal (i.p.) treatment with three different doses of L-DOPA/benserazide (30/12.5, 50/25, or 70/35 mg/kg) during 3 weeks induced increasing levels of LID scores in hemiparkinsonian Swiss albino mice previously lesioned with a unilateral intrastriatal injection of 6-hydroxydopamine (6-OHDA, 10 μg). Then, we addressed the antidyskinetic effects of treadmill-controlled exercise by comparing LID, induced by L-DOPA/benserazide (50/25 mg/kg, i.p.) during 4 weeks, in sedentary and daily exercised mice. Exercise reduced LID and improved motor skills of dyskinetic mice, as indicated by decreased contralateral bias, increase in maximal load test, and latency to fall in rotarod. The antidyskinetic effect of amantadine (60 mg/kg, i.p.) was only observed in sedentary mice, indicating the absence of synergistic antidyskinetic effect of the combination of treadmill exercise plus amantadine. Finally, Western blot analysis unraveled an ability of exercise to increase the striatal immunocontent of glial cell-derived neurotrophic factor (GDNF), apart from normalizing striatal levels of tyrosine hydroxylase. These findings show that controlled treadmill exercise attenuates LID and provide the first indication that the antidyskinetic effects of treadmill exercise may involve increased striatal GDNF levels.
Mindfulness-based cognitive therapy v. treatment as usual in adults with ADHD: a multicentre, single-blind, randomised controlled trial.
Psychological medicine, 2019

There is a high need for evidence-based psychosocial treatments for adult attention-deficit hyperactivity disorder (ADHD) to offer alongside treatment as usual (TAU). Mindfulness-based cognitive therapy (MBCT) is a promising psychosocial treatment. This trial investigated the efficacy of MBCT + TAU v. TAU in reducing core symptoms in adults with ADHD.
Genetic disruption of the alternative splicing of drebrin gene impairs context-dependent fear learning in adulthood.
Neuroscience, 2010

Dendritic spines are postsynaptic structures at excitatory synapses that play important roles in synaptic transmission and plasticity. Dendritic spine morphology and function are regulated by an actin-based cytoskeletal network. Drebrin A, an adult form of drebrin, is an actin-binding protein in dendritic spines, and its decrease is purportedly concerned with synaptic dysfunction in Alzheimer's disease. Rapid conversion of drebrin E, an embryonic form of drebrin, to drebrin A occurs in parallel with synaptic maturation. To understand the physiological role of drebrin isoform conversion in vivo, we generated knockout mice in which a drebrin A-specific exon was deleted from the drebrin gene. Drebrin A-specific knockout (DAKO) mice expressed drebrin E, which substituted for drebrin A. Subcellular fractionation experiment indicated that cytosolic form of drebrin was increased in the brains of DAKO mice. Furthermore, drebrin accumulation in synaptosomes of DAKO mice was much higher than that of wild-type (WT) mice. DAKO mice were viable and showed no apparent abnormalities in their gross brain morphology and general behaviors. However, DAKO mice were impaired in a context-dependent freezing after fear conditioning. These data indicate that drebrin A plays an indispensable role in some processes of generating fear learning and memory.
Adenosine A(2A) receptor blockade reverts hippocampal stress-induced deficits and restores corticosterone circadian oscillation.
Molecular psychiatry, 2013

Maternal separation (MS) is an early life stress model that induces permanent changes in the central nervous system, impairing hippocampal long-term potentiation (LTP) and spatial working memory. There are compelling evidences for a role of hippocampal adenosine A(2A) receptors in stress-induced modifications related to cognition, thus opening a potential window for therapeutic intervention. Here, we submitted rats to MS and evaluated the long-lasting molecular, electrophysiological and behavioral impairments in adulthood. We then assessed the therapeutic potential of KW6002, a blocker of A(2A) receptors, in stress-impaired animals. We report that the blockade of A(2A) receptors was efficient in reverting the behavior, electrophysiological and morphological impairments induced by MS. In addition, this effect is associated with restoration of the hypothalamic-pituitary-adrenal axis (HPA-axis) activity, as both the plasma corticosterone levels and hippocampal glucocorticoid receptor expression pattern returned to physiological-like status after the treatment. These results reveal the involvement of A(2A) receptors in the stress-associated impairments and directly in the stress response system by showing that the dysfunction of the HPA-axis as well as the long-lasting synaptic and behavioral effects of MS can be reverted by targeting adenosine A(2A) receptors. These findings provide a novel evidence for the use of adenosine A(2A) receptor antagonists as potential therapy against psychopathologies.
The burden of premature mortality of epilepsy in high-income countries: A systematic review from the Mortality Task Force of the International League Against Epilepsy.
Epilepsia, 2017

Since previous reviews of epidemiologic studies of premature mortality among people with epilepsy were completed several years ago, a large body of new evidence about this subject has been published. We aim to update prior reviews of mortality in epilepsy and to reevaluate and quantify the risks, potential risk factors, and causes of these deaths. We systematically searched the Medline and Embase databases to identify published reports describing mortality risks in cohorts and populations of people with epilepsy. We reviewed relevant reports and applied criteria to identify those studies likely to accurately quantify these risks in representative populations. From these we extracted and summarized the reported data. All population-based studies reported an increased risk of premature mortality among people with epilepsy compared to general populations. Standard mortality ratios are especially high among people with epilepsy aged <50 years, among those whose epilepsy is categorized as structural/metabolic, those whose seizures do not fully remit under treatment, and those with convulsive seizures. Among deaths directly attributable to epilepsy or seizures, important immediate causes include sudden unexpected death in epilepsy (SUDEP), status epilepticus, unintentional injuries, and suicide. Epilepsy-associated premature mortality imposes a significant public health burden, and many of the specific causes of death are potentially preventable. These require increased attention from healthcare providers, researchers, and public health professionals.
Sustained effects of incredible years as a preventive intervention in preschool children with conduct problems.
Journal of abnormal child psychology, 2012

The present study evaluated preventive effects of the Incredible Years program for parents of preschool children who were at risk for a chronic pattern of conduct problems, in the Netherlands. In a matched control design, 72 parents of children with conduct problems received the Incredible Years program. These families (intervention group) were compared with 72 families who received care as usual (control group). Two years after termination of the intervention, it appeared that observed and selfrated parenting skills were significantly improved in the intervention group. Likewise, in this group, observed child conduct problems showed sustained intervention effects. The decrease in observed critical parenting mediated the decrease in observed child conduct problems over time. In addition, it appeared that parental influence increased over time.
Evidence for motivational effects elicited by activation of GABA-A or dopamine receptors in the nucleus accumbens shell.
Pharmacology, biochemistry, and behavior, 2010

Microinjections of the inhibitory GABA-A receptor agonist muscimol into the shell region of the nucleus accumbens (AcbSh) have been reported to induce large increases in food intake, but the effect of these injections on motivational processes is less clear. In the current study, bilateral injections of saline, muscimol (50ng/side) or d-amphetamine (10mug/side) were made into the AcbSh of rats trained to lever press on a progressive ratio schedule for food reward. Injections of both muscimol and amphetamine were found to produce a large increase in the breaking point relative to saline injections. This result suggests that inactivation of the AcbSh does not simply drive ingestive behavior, but also affects motivational processes assessed by the progressive ratio schedule. Breaking points were also increased by injections of amphetamine into the AcbSh.
Endogenous morphine levels are increased in sepsis: a partial implication of neutrophils.
PloS one, 2010

Mammalian cells synthesize morphine and the respective biosynthetic pathway has been elucidated. Human neutrophils release this alkaloid into the media after exposure to morphine precursors. However, the exact role of endogenous morphine in inflammatory processes remains unclear. We postulate that morphine is released during infection and can be determined in the serum of patients with severe infection such as sepsis.
Breastfeeding and Childhood IQ: The Mediating Role of Gray Matter Volume.
Journal of the American Academy of Child and Adolescent Psychiatry, 2016

A substantial body of literature has established the positive effect of breastfeeding on child developmental outcomes. There is increasing consensus that breastfed children have higher IQs after accounting for key variables, including maternal education, IQ, and socioeconomic status. Cross-sectional investigations of the effects of breastfeeding on structural brain development suggest that breastfed infants have larger whole brain, cortical, and white matter volumes. To date, few studies have related these measures of brain structure to IQ in breastfed versus nonbreastfed children in a longitudinal sample.
Tryptophan and kynurenines: continuing to court controversy.
Clinical science (London, England : 1979), 2016

The role of the amino acid tryptophan in the generation of 5-hydroxy-tryptamine (5-HT) has been expanded over the past 30 years with recognition that its oxidation by indoleamine-2,3-dioxygenase (IDO) results in the formation of kynurenine and metabolites which regulate neuronal excitability, psychiatric status, immune cell activity and balance, and probably implantation and the development of embryos. While the amount of work on this kynurenine pathway continues to accelerate, it is important that disagreements about results, differences of interpretation or problems with technical issues are presented openly and discussed thoroughly so that new research is not mis-led in ways that could have been foreseen. In this issue of Clinical Science, Badawy et al. discuss in depth two opposing views of how changes in tryptophan availability or utilisation bring about their effects on cell function. The original concept that local depletion of tryptophan is responsible seems to be less attractive than the view that kynurenine and its metabolites have direct, potent actions on cells. This conclusion not only clarifies our understanding of the importance of tryptophan metabolism to kynurenine but also raises the possibility that the actions of those metabolites could be novel targets for the development of agonists and antagonists with a range of medical implications.
Relaxin-3 receptor (RXFP3) activation in the nucleus of the solitary tract modulates respiratory rate and the arterial chemoreceptor reflex in rat.
Respiratory physiology & neurobiology, 2020

The neuropeptide relaxin-3 is expressed by the pontine nucleus incertus. Relaxin-3 and synthetic agonist peptides modulate arousal and cognitive processes via activation of the relaxin-family peptide 3 receptor (RXFP3). Despite the presence of RXFP3 in the nucleus of the solitary tract (NTS), the ability of RXFP3 to modulate NTS-mediated cardiorespiratory functions has not been explored. Therefore, we examined the effects of bilateral microinjections of the selective agonist, RXFP3-A2 (40 μM, 100 nL/side), into the NTS in perfused working-heart-brainstem-preparations from rats (n = 6), while recording phrenic, vagal, and thoracic sympathetic chain activity (PNA, VNA, t-SCA) and heart rate (HR). RXFP3-A2 significantly increased respiratory rate and shortened post-inspiratory VNA. RXFP3-A2 in the NTS also significantly enhanced arterial chemoreceptor reflex (a-CR)-mediated tachypnea. However, RXFP3-A2 had no significant effect on HR and t-SCA at baseline or during the a-CR. These data represent the first evidence that RXFP3 activation in the NTS can selectively modulate respiration at baseline and during reflex behaviour.
Accuracy of Point-of-Care Blood Glucose Level Measurements in Critically Ill Patients with Sepsis Receiving High-Dose Intravenous Vitamin C.
Pharmacotherapy, 2018

High-dose intravenous vitamin C is a potential treatment option for patients with sepsis and may interfere with point-of-care (POC) blood glucose (BG) testing. This study aimed to determine if vitamin C dosing used for sepsis affected POC BG level results.
Molecular neurobiology of bipolar disorder: a disease of 'mood-stabilizing neurons'?
Trends in neurosciences, 2008

Although the role of a genetic factor is established in bipolar disorder, causative genes or robust genetic risk factors have not been identified. Increased incidence of subcortical hyperintensity, altered calcium levels in cells derived from patients and neuroprotective effects of mood stabilizers suggest vulnerability or impaired resilience of neurons in bipolar disorder. Mitochondrial dysfunction or impaired endoplasmic reticulum stress response is suggested to play a role in the neurons' vulnerability. Progressive loss or dysfunction of 'mood-stabilizing neurons' might account for the characteristic course of the illness. The important next step in the neurobiological study of bipolar disorder is identification of the neural systems that are responsible for this disorder.
Atomic level characterization of the nonproton ligand-sensing domain of ASIC3 channels.
The Journal of biological chemistry, 2011

Acid-sensing ion channels (ASICs) are known to be primarily activated by extracellular protons. Recently, we characterized a novel nonproton ligand (2-guanidine-4-methylquinazoline, GMQ), which activates the ASIC3 channel subtype at neutral pH. Using an interactive computational-experimental approach, here we extend our investigation to delineate the architecture of the GMQ-sensing domain in the ASIC3 channels. We first established a GMQ binding mode and revealed that residues Glu-423, Glu-79, Leu-77, Arg-376, Gln-271, and Gln-269 play key roles in forming the GMQ-sensing domain. We then verified the GMQ binding mode using ab initio calculation and mutagenesis and demonstrated the critical role of the above GMQ-binding residues in the interplay among GMQ, proton, and Ca(2+) in regulating the function of ASIC3. Additionally, we showed that the same residues involved in coordinating GMQ responses are also critical for activation of the ASIC3(E79C) mutant by thiol-reactive compound DTNB. Thus, a range of complementary techniques provide independent evidence for the structural details of the GMQ-sensing domain at atomic level, laying the foundation for further investigations of endogenous nonproton ligands and gating mechanisms of the ASIC3 channels.
High performance communication by people with paralysis using an intracortical brain-computer interface.
eLife, 2017

Brain-computer interfaces (BCIs) have the potential to restore communication for people with tetraplegia and anarthria by translating neural activity into control signals for assistive communication devices. While previous pre-clinical and clinical studies have demonstrated promising proofs-of-concept (Serruya et al., 2002; Simeral et al., 2011; Bacher et al., 2015; Nuyujukian et al., 2015; Aflalo et al., 2015; Gilja et al., 2015; Jarosiewicz et al., 2015; Wolpaw et al., 1998; Hwang et al., 2012; Spüler et al., 2012; Leuthardt et al., 2004; Taylor et al., 2002; Schalk et al., 2008; Moran, 2010; Brunner et al., 2011; Wang et al., 2013; Townsend and Platsko, 2016; Vansteensel et al., 2016; Nuyujukian et al., 2016; Carmena et al., 2003; Musallam et al., 2004; Santhanam et al., 2006; Hochberg et al., 2006; Ganguly et al., 2011; O'Doherty et al., 2011; Gilja et al., 2012), the performance of human clinical BCI systems is not yet high enough to support widespread adoption by people with physical limitations of speech. Here we report a high-performance intracortical BCI (iBCI) for communication, which was tested by three clinical trial participants with paralysis. The system leveraged advances in decoder design developed in prior pre-clinical and clinical studies (Gilja et al., 2015; Kao et al., 2016; Gilja et al., 2012). For all three participants, performance exceeded previous iBCIs (Bacher et al., 2015; Jarosiewicz et al., 2015) as measured by typing rate (by a factor of 1.4-4.2) and information throughput (by a factor of 2.2-4.0). This high level of performance demonstrates the potential utility of iBCIs as powerful assistive communication devices for people with limited motor function.Clinical Trial No: NCT00912041.
Reactive Oxygen Species Are Key Mediators of Demyelination in Canine Distemper Leukoencephalitis but not in Theiler's Murine Encephalomyelitis.
International journal of molecular sciences, 2019

(1) Background: Canine distemper virus (CDV)-induced demyelinating leukoencephalitis (CDV-DL) in dogs and Theiler's murine encephalomyelitis (TME) virus (TMEV)-induced demyelinating leukomyelitis (TMEV-DL) are virus-induced demyelinating conditions mimicking Multiple Sclerosis (MS). Reactive oxygen species (ROS) can induce the degradation of lipids and nucleic acids to characteristic metabolites such as oxidized lipids, malondialdehyde, and 8-hydroxyguanosine. The hypothesis of this study is that ROS are key effector molecules in the pathogenesis of myelin membrane breakdown in CDV-DL and TMEV-DL. (2) Methods: ROS metabolites and antioxidative enzymes were assessed using immunofluorescence in cerebellar lesions of naturally CDV-infected dogs and spinal cord tissue of TMEV-infected mice. The transcription of selected genes involved in ROS generation and detoxification was analyzed using gene-expression microarrays in CDV-DL and TMEV-DL. (3) Results: Immunofluorescence revealed increased amounts of oxidized lipids, malondialdehyde, and 8-hydroxyguanosine in CDV-DL while TMEV-infected mice did not reveal marked changes. In contrast, microarray-analysis showed an upregulated gene expression associated with ROS generation in both diseases. (4) Conclusion: In summary, the present study demonstrates a similar upregulation of gene-expression of ROS generation in CDV-DL and TMEV-DL. However, immunofluorescence revealed increased accumulation of ROS metabolites exclusively in CDV-DL. These results suggest differences in the pathogenesis of demyelination in these two animal models.