rudyvdbrink/CitationDatabase huggingface dataset:
Age-related changes in murine bladder structure and sensory innervation: a multiphoton microscopy quantitative analysis.
Age (Dordrecht, Netherlands), 2016

Our study aimed to examine and quantify age-related structural alterations in the healthy mouse bladder using ex vivo two-photon laser scanning microscopy (TPLSM). Freshly dissected bladders from 25-, 52-, and 85-week-old C57bl/6J mice were examined, and morphological analyses and quantification of cell layers and nerves were performed. The numbers of stretched, curled, branched, and total number of nerves in volume units of the stained muscle layer were quantified. We observed differences in the bladder wall architecture and innervation with age. Especially in 85-week-old mice, age-related changes were found, including detachment of urothelial cells and an increase in connective tissue, intermingled with the smooth muscle fibers in the muscle layer (collagen-smooth muscle ratio of 1.15 ± 0.29). In 25- and 52-week-old mice, the collagen-smooth muscle ratios were 0.20 ± 0.04 and 0.31 ± 0.11, respectively, and a clear separation of collagen and muscle was observed. The overall number of nerves and the number of curled nerves were significantly higher in the 85-week-old mice (74.0 ± 13.0 and 25.9 ± 4.8, respectively), when comparing to 25-week-old mice (26.0 ± 2.7 and 6.7 ± 1.2, respectively) and 52-week-old mice (43.8 ± 4.3 and 22.1 ± 3.3, respectively). Significant age-related alterations in bladder morphology and innervation were found, when comparing freshly dissected bladder tissue from 25-, 52-, and 85-week-old mice. The higher number of curled nerves might be an indication of an increased neurotransmitter release, resulting in a higher nerve activity, with a part of the nerves being possibly mechanically impaired. This study shows that two-photon laser scanning microscopy of healthy aging male mice is a useful method to investigate and quantify the age-related changes in the bladder wall.
Intervention versus standard medical treatment in patients with symptomatic occlusion of the internal carotid artery: a randomised oxygen-15 PET study.
EJNMMI research, 2013

The aim of this randomised pilot study was to investigate the haemodynamic effects measured by oxygen-15 positron emission tomography (PET) of interventional treatment consisting of either endarterectomy or endovascular treatment of stenosed cerebropetal arteries, or tapering of antihypertensive medication in comparison with standard medical treatment alone in patients with symptomatic internal carotid artery (ICA) occlusion.
The effects of choice on intrinsic motivation and related outcomes: a meta-analysis of research findings.
Psychological bulletin, 2008

A meta-analysis of 41 studies examined the effect of choice on intrinsic motivation and related outcomes in a variety of settings with both child and adult samples. Results indicated that providing choice enhanced intrinsic motivation, effort, task performance, and perceived competence, among other outcomes. Moderator tests revealed the effect of choice on intrinsic motivation was stronger (a) for instructionally irrelevant choices compared to choices made between activities, versions of a task, rewards, and instructionally relevant options, (b) when 2 to 4 successive choices were given, (c) when rewards were not given after the choice manipulation, (d) when participants given choice were compared to the most controlling forms of control groups, (e) for children compared to adults, (f) for designs that yoked choice and control conditions compared to matched designs in which choice was reduced or designs in which nonyoked, nonmatched controls were used, and (g) when the experiment was conducted in a laboratory embedded in a natural setting. Implications for future research and applications to real-world settings are discussed.
Sleep and REM sleep behaviour disorder in Parkinson's disease with impulse control disorder.
Journal of neurology, neurosurgery, and psychiatry, 2018

Because the association between rapid eye movement sleep behaviour disorder (RBD) and impulse control disorders (ICDs) in Parkinson's disease (PD) has been debated, we assessed the sleep characteristics and the frequency of RBD using video-polysomnography (v-PSG) in patients with PD with versus without ICDs.
Expression of the core exon-junction complex factor eukaryotic initiation factor 4A3 is increased during spatial exploration and striatally-mediated learning.
Neuroscience, 2012

Regulation of dendritically localized mRNAs offers an important means by which neurons can sculpt precise signals at synapses. Arc is one such dendritically localized mRNA, and it has been shown to contain two exon-junction complexes (EJCs) within its 3'UTR. The EJC has been postulated to regulate cytoplasmic Arc mRNA availability through translation-dependent decay and thus contribute to synaptic plasticity. Core proteins of the EJC include eIF4A3, an RNA helicase, and Magoh, which stabilizes the interaction of eIF4A3 with target mRNAs. Arc mRNA expression is activity-regulated in numerous brain regions, including the dorsal striatum and hippocampus. Therefore in this study, the in vivo expression of these core EJC components was investigated in adult Sprague-Dawley rats to determine whether there are also behaviorally regulated changes in their expression. In the present work, there was no change in the expression of Magoh mRNA following spatial exploration, a paradigm previously reported to robustly and reliably upregulate Arc mRNA expression. Interestingly, however, there were increases in eIF4A3 mRNA levels in the dorsal striatum and hippocampus following spatial exploration, similar to previous reports for Arc mRNA. Furthermore, there were activity-dependent changes in eIF4A3 protein distribution and expression within the striatum following spatial exploration. Importantly, eIF4A3 protein colocalized with Arc mRNA in vivo. Like Arc mRNA expression, eIF4A3 mRNA expression in the dorsomedial striatum, but not dorsolateral striatum or hippocampus, significantly correlated with behavioral performance on a striatally-mediated, response-reversal learning task. This study provides direct evidence that a core EJC component, eIF4A3, shows activity-dependent changes in both mRNA and protein expression in the adult mammalian brain. These findings thus further implicate eIF4A3 as a key mediator of Arc mRNA availability underlying learning and memory processes in vivo.
Creation of a bi-directional protein transduction system for suppression of HIV-1 expression by p27SJ.
Antiviral research, 2008

p27SJ is a novel protein from a callus culture of St. John's wort that modulates transcription of the HIV-1 promoter in several mammalian cells [Darbinian-Sarkissian, N., Darbinyan, A., Otte, J., Radhakrishnan, S., Sawaya, B.E., Arzumanyan, A., Chipitsyna, G., Popov, Y., Rappaport, J., Amini, S., Khalili, K., 2006. p27(SJ), a novel protein from St. John's wort, that suppresses expression of HIV-1 genome. Gene Ther. 13, 288-295]. Here, we armed p27SJ with signals from Ig-kappa light chain that allow its efficient excretion from the cells, and from HIV-1 Tat that facilitates its uptake by other cells for its utilization by a protein transduction method. We demonstrate that treatment of cells containing the HIV-1 LTR with conditioned media from cells expressing the armed p27SJ ((exc)p27SJ(upt)) results in suppression of the viral activation by the C/EBPbeta transcription factor. Once imported into the cells, (exc)p27SJ(upt) impacts the nuclear localization of C/EBPbeta and by retaining the protein in the cytoplasm affects its DNA binding and hence transcriptional activity. The armed p27SJ also inhibits Tat-induced activation of the LTR and decreases the level of viral replication in promonocytic cells including U-937 and T-lymphocytic cells. Our observations introduce a new bi-directional protein transduction system with a broad spectrum of applications for manufacturing therapeutic peptides by a specific group of cells called donor, and delivery to the target cells named recipient. Furthermore, our results support the utility of soluble p27SJ in suppressing transcription and replication of HIV-1 by interfering with the function of cellular proteins such as C/EBPbeta and viral activators including Tat.
Respiratory infection promotes T cell infiltration and amyloid-β deposition in APP/PS1 mice.
Neurobiology of aging, 2014

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by deposits of amyloid-β and neurofibrillary tangles. It has been suggested that inflammatory changes are associated with disease; however, it has not been established whether these are a consequence of ongoing neurodegeneration or whether inflammation itself contributes to disease pathogenesis. Recent studies suggest that exposure to infection can accelerate cognitive decline in AD patients, and pathogens have been detected in the AD brain. However, the influence of infection on neuroinflammation and pathology remains poorly understood. In this study, we examined the effect of a peripheral infection on AD pathology in APP/PS1 mice. We found that, 8 weeks after infection with the Gram negative respiratory pathogen Bordetella pertussis, there was significant infiltration of IFNγ- and IL-17-producing T cells and NKT cells in older APP/PS1 mice. This was accompanied by increased glial activation and amyloid-β deposition. The data suggest that infection is a critical factor in the progression of AD, emphasising the importance of early diagnosis and treatment of infections in elderly individuals.
Individual differences in the time course of reward processing: Stage-specific links with depression and impulsivity.
Biological psychology, 2016

Reward dysfunction has been implicated in a wide range of psychological disorders, including internalizing and externalizing psychopathology. Basic neuroscience research has shown that reward is a multistage process, yet it is unclear how specific stages relate to individual differences in reward sensitivity. The current study utilized event-related potentials elicited during a monetary incentive task to parse sub-stages within anticipatory and consummatory reward processing. Effects of depressive symptoms and trait impulsivity were examined at each sub-stage (N=92). Reward anticipation modulated neural activity across three sub-stages: cue detection (cue-P3), approach behavior (contingent negative variation, CNV), and outcome anticipation (stimulus preceding negativity). Reward delivery modulated activity across two sub-stages: initial evaluation (reward positivity, RewP), and allocation of attention (feedback-P3). Sensation seeking predicted faster reaction times, as well as cue-P3 and RewP amplitudes. Depression and lack of premeditation interacted to predict CNV and RewP amplitudes. Results demonstrate that individual differences in reward functioning are stage-specific.
Glutamate in schizophrenia: Neurodevelopmental perspectives and drug development.
Schizophrenia research, 2020

Research into the neurobiological processes that may lead to the onset of schizophrenia places growing emphasis on the glutamatergic system and brain development. Preclinical studies have shown that neurodevelopmental, genetic, and environmental factors contribute to glutamatergic dysfunction and schizophrenia-related phenotypes. Clinical research has suggested that altered brain glutamate levels may be present before the onset of psychosis and relate to outcome in those at clinical high risk. After psychosis onset, glutamate dysfunction may also relate to the degree of antipsychotic response and clinical outcome. These findings support ongoing efforts to develop pharmacological interventions that target the glutamate system and could suggest that glutamatergic compounds may be more effective in specific patient subgroups or illness stages. In this review, we consider the updated glutamate hypothesis of schizophrenia, from a neurodevelopmental perspective, by reviewing recent preclinical and clinical evidence, and discuss the potential implications for novel therapeutics.
Facilitation of brain mitochondrial activity by 5-aminolevulinic acid in a mouse model of Alzheimer's disease.
Nutritional neuroscience, 2017

The activities of mitochondrial enzymes, which are essential for neural function, decline with age and in age-related disease. In particular, the activity of cytochrome c oxidase (COX/complex IV) decreases in patients with Alzheimer's disease (AD). COX, a mitochondrial inner membrane protein complex that contains heme, plays an essential role in the electron transport chain that generates ATP. Heme synthesis begins with 5-aminolevulinic acid (5-ALA) in mitochondria. 5-ALA synthetase is the rate-limiting enzyme in heme synthesis, suggesting that supplementation with 5-ALA might help preserve mitochondrial activity in the aged brain. We administered a diet containing 5-ALA to triple-transgenic AD (3xTg-AD) model mice for 6 months, starting at 3 months of age. COX activity and protein expression, as well as mitochondrial membrane potential, were significantly higher in brains of 5-ALA-fed mice than in controls. Synaptotagmin protein levels were also significantly higher in 5-ALA-fed mice, suggesting improved preservation of synapses. Although brain Aβ levels tended to decrease in 5-ALA-fed mice, we observed no other significant changes in other biochemical and pathological hallmarks of AD. Nevertheless, our study suggests that daily oral administration of 5-ALA could preserve mitochondrial enzyme activities in the brains of aged individuals, thereby contributing to the preservation of neural activity.
Rescue of deficient amygdala tonic γ-aminobutyric acidergic currents in the Fmr-/y mouse model of fragile X syndrome by a novel γ-aminobutyric acid type A receptor-positive allosteric modulator.
Journal of neuroscience research, 2016

Alterations in the ratio of excitatory to inhibitory transmission are emerging as a common component of many nervous system disorders, including autism spectrum disorders (ASDs). Tonic γ-aminobutyric acidergic (GABAergic) transmission provided by peri- and extrasynaptic GABA type A (GABAA ) receptors powerfully controls neuronal excitability and plasticity and, therefore, provides a rational therapeutic target for normalizing hyperexcitable networks across a variety of disorders, including ASDs. Our previous studies revealed tonic GABAergic deficits in principal excitatory neurons in the basolateral amygdala (BLA) in the Fmr1(-/y) knockout (KO) mouse model fragile X syndrome. To correct amygdala deficits in tonic GABAergic neurotransmission in Fmr1(-/y) KO mice, we developed a novel positive allosteric modulator of GABAA receptors, SGE-872, based on endogenously active neurosteroids. This study shows that SGE-872 is nearly as potent and twice as efficacious for positively modulating GABAA receptors as its parent molecule, allopregnanolone. Furthermore, at submicromolar concentrations (≤1 μM), SGE-872 is selective for tonic, extrasynaptic α4β3δ-containing GABAA receptors over typical synaptic α1β2γ2 receptors. We further find that SGE-872 strikingly rescues the tonic GABAergic transmission deficit in principal excitatory neurons in the Fmr1(-/y) KO BLA, a structure heavily implicated in the neuropathology of ASDs. Therefore, the potent and selective action of SGE-872 on tonic GABAA receptors containing α4 subunits may represent a novel and highly useful therapeutic avenue for ASDs and related disorders involving hyperexcitability of neuronal networks.
Body posture differentially impacts on visual attention towards tool, graspable, and non-graspable objects.
Journal of experimental psychology. Human perception and performance, 2017

Viewed objects have been shown to afford suitable actions, even in the absence of any intention to act. However, little is known as to whether gaze behavior (i.e., the way we simply look at objects) is sensitive to action afforded by the seen object and how our actual motor possibilities affect this behavior. We recorded participants' eye movements during the observation of tools, graspable and ungraspable objects, while their hands were either freely resting on the table or tied behind their back. The effects of the observed object and hand posture on gaze behavior were measured by comparing the actual fixation distribution with that predicted by 2 widely supported models of visual attention, namely the Graph-Based Visual Saliency and the Adaptive Whitening Salience models. Results showed that saliency models did not accurately predict participants' fixation distributions for tools. Indeed, participants mostly fixated the action-related, functional part of the tools, regardless of its visual saliency. Critically, the restriction of the participants' action possibility led to a significant reduction of this effect and significantly improved the model prediction of the participants' gaze behavior. We suggest, first, that action-relevant object information at least in part guides gaze behavior. Second, postural information interacts with visual information to the generation of priority maps of fixation behavior. We support the view that the kind of information we access from the environment is constrained by our readiness to act. (PsycINFO Database Record
Interaction between μ-opioid and 5-HT1A receptors in the regulation of panic-related defensive responses in the rat dorsal periaqueductal grey.
Journal of psychopharmacology (Oxford, England), 2014

A wealth of evidence indicates that the activation of 5-HT1A and 5-HT2A receptors in the dorsal periaqueductal grey matter (dPAG) inhibits escape, a panic-related defensive behaviour. Results that were previously obtained with the elevated T-maze test of anxiety/panic suggest that 5-HT1A and μ-opioid receptors in this midbrain area work together to regulate this response. To investigate the generality of this finding, we assessed whether the same cooperative mechanism is engaged when escape is evoked by a different aversive stimulus electrical stimulation of the dPAG. Administration of the μ-receptor blocker CTOP into the dPAG did not change the escape threshold, but microinjection of the μ-receptor agonist DAMGO (0.3 and 0.5 nmol) or the 5-HT1A receptor agonist 8-OHDPAT (1.6 nmol) increased this index, indicating a panicolytic-like effect. Pretreatment with CTOP antagonised the anti-escape effect of 8-OHDPAT. Additionally, combined administration of subeffective doses of DAMGO and 8-OHDPAT increased the escape threshold, indicating drug synergism. Therefore, regardless of the aversive nature of the stimulus, μ-opioid and 5-HT1A receptors cooperatively act to regulate escape behaviour. A better comprehension of this mechanism might allow for new therapeutic strategies for panic disorder.
Mitochondrial DNA Analysis from Exome Sequencing Data Improves Diagnostic Yield in Neurological Diseases.
Annals of neurology, 2021

A rapidly expanding catalog of neurogenetic disorders has encouraged a diagnostic shift towards early clinical whole exome sequencing (WES). Adult primary mitochondrial diseases (PMDs) frequently exhibit neurological manifestations that overlap with other nervous system disorders. However, mitochondrial DNA (mtDNA) is not routinely analyzed in standard clinical WES bioinformatic pipelines. We reanalyzed 11,424 exomes, enriched with neurological diseases, for pathogenic mtDNA variants. Twenty-four different mtDNA mutations were detected in 64 exomes, 11 of which were considered disease causing based on the associated clinical phenotypes. These findings highlight the diagnostic uplifts gained by analyzing mtDNA from WES data in neurological diseases. ANN NEUROL 2021;89:1240-1247.
p35 and Rac1 underlie the neuroprotection and cognitive improvement induced by CDK5 silencing.
Journal of neurochemistry, 2015

CDK5 plays an important role in neurotransmission and synaptic plasticity in the normal function of the adult brain, and dysregulation can lead to Tau hyperphosphorylation and cognitive impairment. In a previous study, we demonstrated that RNAi knock down of CDK5 reduced the formation of neurofibrillary tangles (NFT) and prevented neuronal loss in triple transgenic Alzheimer's mice. Here, we report that CDK5 RNAi protected against glutamate-mediated excitotoxicity using primary hippocampal neurons transduced with adeno-associated virus 2.5 viral vector eGFP-tagged scrambled or CDK5 shRNA-miR during 12 days. Protection was dependent on a concomitant increase in p35 and was reversed using p35 RNAi, which affected the down-stream Rho GTPase activity. Furthermore, p35 over-expression and constitutively active Rac1 mimicked CDK5 silencing-induced neuroprotection. In addition, 3xTg-Alzheimer's disease mice (24 months old) were injected in the hippocampus with scrambled or CDK5 shRNA-miR, and spatial learning and memory were performed 3 weeks post-injection using 'Morris' water maze test. Our data showed that CDK5 knock down induced an increase in p35 protein levels and Rac activity in triple transgenic Alzheimer's mice, which correlated with the recovery of cognitive function; these findings confirm that increased p35 and active Rac are involved in neuroprotection. In summary, our data suggest that p35 acts as a mediator of Rho GTPase activity and contributes to the neuroprotection induced by CDK5 RNAi.
The impact of DSM-5 on the diagnosis and severity indicator of eating disorders in a treatment-seeking sample.
The International journal of eating disorders, 2017

To examine the impact of the DSM-5 on the diagnoses and severity indicators of eating disorders, we conducted a comparative study on the classification of eating disorders including subtypes of anorexia nervosa (AN) between the DSM-IV and DSM-5 criteria. In addition, we studied the association of the DSM-5 severity criteria and clinical variables.
Newborn dopaminergic neurons are associated with the migration and differentiation of SVZ-derived neural progenitors in a 6-hydroxydopamin-injected mouse model.
Neuroscience, 2017

The use of the existing endogenous neural progenitor cells (NPCs) in the brains of adult mammalian animals is challenging for cell therapy in treating Parkinson's disease (PD). Previous studies have indicated that there is a low level of neurogenesis in the substantia nigra (SN) of adult mice. To assess the regenerative/neurogenic capacity of NPCs following an intranigral injection of 6-hydroxydopamine (6-OHDA), the proliferation and differentiation of subventricular zone (SVZ)- and midbrain-derived NPCs were investigated, and the origin of SN newborn dopaminergic neurons was traced by using Nestin-CreER
Application of diffusion tensor imaging in multiple system atrophy: the involvement of pontine transverse and longitudinal fibers.
The International journal of neuroscience, 2015

Many studies have demonstrated the degeneration of pontine transverse and longitudinal tracts in multiple system atrophy (MSA). One purpose of this study was to assess whether diffusion tensor imaging (DTI) can show microstructural abnormalities in these tracts in patients with MSA cerebellar type (MSA-C). Another purpose was to determine the correlation between cross sign progress and pontine fiber degeneration in these patients.