rudyvdbrink/CitationDatabase huggingface dataset:
Quercetin Attenuates Decrease of Thioredoxin Expression Following Focal Cerebral Ischemia and Glutamate-induced Neuronal Cell Damage.
Neuroscience, 2020

Quercetin is a bioactive flavonoid which abundantly exists in vegetables and fruits. Quercetin exerts a neuroprotective effect against cerebral ischemia. Thioredoxin acts as antioxidant by regulating redox signaling. This study investigated whether quercetin regulates thioredoxin expression in focal cerebral ischemia and glutamate-induced neuronal cell death. Male Sprague Dawley rats (210-230 g) were intraperitoneally injected with vehicle or quercetin (10 mg/kg) 1 h prior to middle cerebral artery occlusion (MCAO). Cerebral cortex was collected 24 h after MCAO. MCAO led to neurological movement deficits, brain edema, and serious histopathological damages in cerebral cortex, and quercetin alleviated these damages following MCAO. We observed the change of thioredoxin expression in MCAO animals with quercetin using proteomic approach, reverse-transcription PCR, and Western blot analyses. Thioredoxin expression decreased in vehicle-treated MCAO animals, while quercetin attenuated this decrease. Moreover, quercetin treatment alleviated the decrease in the number of thioredoxin-positive cells in cerebral cortex of MCAO animals. Furthermore, immunoprecipitation analysis demonstrated that interaction of apoptosis signal-regulating kinase 1 (ASK1) and thioredoxin was decreased in MCAO animals with vehicle, while quercetin prevented MCAO-induced decrease in these binding. In addition, quercetin also alleviated the reduction of cell viability and the decrease in thioredoxin expression in glutamate-treated hippocampal cell line and primary cultures of cortical neurons. However in thioredoxin-silenced cortical neuron, anti-apoptotic effect of quercetin was decreased. Thus, changes of thioredoxin expression by quercetin may contribute to the neuroprotective effect of quercetin in focal cerebral ischemia. Our findings suggest that quercetin mediates its neuroprotective function by regulation of thioredoxin expression and maintenance of interaction between ASK1 and thioredoxin.
Dopamine receptors regulate NMDA receptor surface expression in prefrontal cortex neurons.
Journal of neurochemistry, 2008

Interactions between dopamine (DA) and glutamate systems in the prefrontal cortex (PFC) are important in addiction and other psychiatric disorders. Here, we examined DA receptor regulation of NMDA receptor surface expression in postnatal rat PFC neuronal cultures. Immunocytochemical analysis demonstrated that surface expression (synaptic and non-synaptic) of NR1 and NR2B on PFC pyramidal neurons was increased by the D1 receptor agonist SKF 81297 (1 microM, 5 min). Activation of protein kinase A (PKA) did not alter NR1 distribution, indicating that PKA does not mediate the effect of D1 receptor stimulation. However, the tyrosine kinase inhibitor genistein (50 microM, 30 min) completely blocked the effect of SKF 81297 on NR1 and NR2B surface expression. Protein cross-linking studies confirmed that SKF 81297 (1 microM, 5 min) increased NR1 and NR2B surface expression, and further showed that NR2A surface expression was not affected. Genistein blocked the effect of SKF 81297 on NR1 and NR2B. Surface-expressed immunoreactivity detected with a phospho-specific antibody to tyrosine 1472 of NR2B also increased after D1 agonist treatment. Our results show that tyrosine phosphorylation plays an important role in the trafficking of NR2B-containing NMDA receptors in PFC neurons and the regulation of their trafficking by DA receptors.
Hyperscanning neuroimaging technique to reveal the "two-in-one" system in social interactions.
Neuroscience research, 2015

Using a technique for measuring brain activity simultaneously from two people, known as hyperscanning, we can calculate inter-brain neural effects that appear only in interactions between individuals. Hyperscanning studies using fMRI are advantageous in that they can precisely determine the region(s) involved in inter-brain effects. However, it is almost impossible to record inter-brain effects in daily life. By contrast, hyperscanning EEG studies have high temporal resolution and could be used to capture moment-to-moment interactions. In addition, EEG instrumentation is portable and easy to wear, offering the opportunity to record inter-brain effects during daily-life interactions. However, the disadvantage of this approach is that it is difficult to localize the epicenter of the inter-brain effect. fNIRS has better temporal resolution and portability than fMRI, but has limited spatial resolution and a limited ability to record deep brain structures. Future studies should employ hyperscanning EEG-fMRI, because this approach combines the high temporal resolution of EEG with the high spatial resolution of fMRI. Hyperscanning EEG-fMRI allows us to use inter-brain effects as neuromarkers of the properties of social interactions in daily life. We also wish to emphasize the need to develop a mathematical model explaining how two brains can exhibit synchronized activity.
Post-stroke patients with moderate function have the greatest risk of falls: a National Cohort Study.
BMC geriatrics, 2019

Stroke patients have increased risks of falls. We examined national registry data to evaluate the association between post-stroke functional level and the risk of low falls among post-stroke patients.
The proline-rich domain promotes Tau liquid-liquid phase separation in cells.
The Journal of cell biology, 2020

Tau protein in vitro can undergo liquid-liquid phase separation (LLPS); however, observations of this phase transition in living cells are limited. To investigate protein state transitions in living cells, we attached Cry2 to Tau and studied the contribution of each domain that drives the Tau cluster in living cells. Surprisingly, the proline-rich domain (PRD), not the microtubule binding domain (MTBD), drives LLPS and does so under the control of its phosphorylation state. Readily observable, PRD-derived cytoplasmic condensates underwent fusion and fluorescence recovery after photobleaching consistent with the PRD LLPS in vitro. Simulations demonstrated that the charge properties of the PRD predicted phase separation. Tau PRD formed heterotypic condensates with EB1, a regulator of plus-end microtubule dynamic instability. The specific domain properties of the MTBD and PRD serve distinct but mutually complementary roles that use LLPS in a cellular context to implement emergent functionalities that scale their relationship from binding α-beta tubulin heterodimers to the larger proportions of microtubules.
Pharmacotherapy for Frontotemporal Dementia.
CNS drugs, 2021

Frontotemporal dementia is a heterogeneous spectrum of neurodegenerative disorders. The neuropathological inclusions are tau proteins, TAR DNA binding protein 43 kDa-TDP-43, or fused in sarcoma-ubiquitinated inclusions. Genetically, several autosomal mutations account for the heritability of the disorder. Phenotypically, frontotemporal dementia can present with a behavioral variant or a language variant called primary progressive aphasia. To date, there are no approved symptomatic or disease-modifying treatments for frontotemporal dementia. Currently used therapies are supported by low-level of evidence (mostly uncontrolled) studies. The off-label use of drugs is also limited by their side-effect profile including an increased risk of confusion, parkinsonian symptoms, and risk of mortality. Emerging disease-modifying treatments currently target the progranulin and the expansion on chromosome 9 open reading frame 72 genes as well as tau deposits. Advancing our understanding of the pathophysiology of the disease and improving the design of future clinical trials are much needed to optimize the chances to obtain positive outcomes.
Opioid receptors: drivers to addiction?
Nature reviews. Neuroscience, 2018

Drug addiction is a worldwide societal problem and public health burden, and results from recreational drug use that develops into a complex brain disorder. The opioid system, one of the first discovered neuropeptide systems in the history of neuroscience, is central to addiction. Recently, opioid receptors have been propelled back on stage by the rising opioid epidemics, revolutions in G protein-coupled receptor research and fascinating developments in basic neuroscience. This Review discusses rapidly advancing research into the role of opioid receptors in addiction, and addresses the key questions of whether we can kill pain without addiction using mu-opioid-receptor-targeting opiates, how mu- and kappa-opioid receptors operate within the neurocircuitry of addiction and whether we can bridge human and animal opioid research in the field of drug abuse.
Tapping polyrhythms in music activates language areas.
Neuroscience letters, 2011

Music is experienced and understood on the basis of foreground/background relationships and tension created between actual music and the underlying meter. Polyrhythms create tension between a counter meter and the main meter. Previously, we have shown that Brodmann area 47 (BA47), a brain area associated with processing of language, is activated bilaterally when musicians tap the main meter in a polymetric context emphasizing a counter meter, suggesting that processing of metric elements in music relies on brain areas also involved in language processing. In that study, the tension was created entirely by changes in the stimulus while participants were tapping the main meter. Here we find left-hemispheric BA47 activation in response to a self-produced counter meter on top of a main meter provided by an ecological music excerpt. This data indicates that the activation is linked to polyrhythmic tension, regardless of whether it arises from the stimulus or the task.
Association between problematic alcohol use and reactivity to uncertain threat in two independent samples.
Drug and alcohol dependence, 2016

Recent laboratory studies have shown that acute alcohol intoxication selectively and effectively dampens aversive responding to uncertain threat. An emerging hypothesis is that individuals who exhibit heightened reactivity to uncertain threat may be especially motivated to use alcohol to dampen their distress, setting the stage for negative reinforcement processes to drive excessive alcohol use. However, no study to date has directly examined whether current problematic drinkers exhibit heightened reactivity to uncertain threat as would be expected.
Molecular basis for differential modulation of BK channel voltage-dependent gating by auxiliary γ subunits.
The Journal of general physiology, 2015

Large conductance Ca(2+)- and voltage-activated potassium (BK) channels are comprised of pore-forming α subunits and various regulatory auxiliary subunits. The BK channel auxiliary γ (BKγ) subunits are a newly identified class of proteins containing an extracellular leucine-rich repeat domain (LRRD), a single transmembrane (TM) segment, and a short cytoplasmic C-terminal tail (C-tail). Although each of the four BKγ proteins shifts the voltage dependence of BK channel activation in a hyperpolarizing direction, they show markedly different efficacies, mediating shifts over a range of 15-145 mV. Analyses of chimeric BKγ subunits created by swapping individual structural elements, and of BKγ deletion and substitution mutants, revealed that differential modulation of BK gating by the four BKγ subunits depends on a small region consisting of the TM segment and the adjacent intracellular cluster of positively charged amino acids. The γ1 and γ2 TM segments contributed approximately -100 mV, and the γ1 and γ3 C-tails contributed approximately -40 mV, to shifting the voltage dependence of BK channel activation, whereas the γ3 and γ4 TM segments and the γ2 and γ4 C-tails contributed much less. The large extracellular LRRDs were mainly functionally interchangeable, although the γ1 LRRD was slightly less effective at enhancing (or slightly more effective at attenuating) the shift in BK channel voltage-dependent gating toward hyperpolarizing potentials than those of the other BKγ subunits. Analysis of mutated BKγ subunits revealed that juxta-membrane clusters of positively charged amino acids determine the functions of the γ1 and γ3 C-tails. Therefore, the modulatory functions of BKγ subunits are coarse- and fine-tuned, respectively, through variations in their TM segments and in the adjacent intracellular positively charged regions. Our results suggest that BK channel modulation by auxiliary γ subunits depends on intra- and/or juxta-membrane mechanisms.
Dysfunctional and compensatory duality in mild cognitive impairment during a continuous recognition memory task.
International journal of psychophysiology : official journal of the International Organization of Psychophysiology, 2013

One of the current issues of debate in the study of mild cognitive impairment (MCI) is deviations of oscillatory brain responses from normal brain states and its dynamics. This work aims to characterize the differences of power in brain oscillations during the execution of a recognition memory task in MCI subjects in comparison with elderly controls. Magnetoencephalographic (MEG) signals were recorded during a continuous recognition memory task performance. Oscillatory brain activity during the recognition phase of the task was analyzed by wavelet transform in the source space by means of minimum norm algorithm. Both groups obtained a 77% hit ratio. In comparison with healthy controls, MCI subjects showed increased theta (p<0.001), lower beta reduction (p<0.001) and decreased alpha and gamma power (p<0.002 and p<0.001 respectively) in frontal, temporal and parietal areas during early and late latencies. Our results point towards a dual pattern of activity (increase and decrease) which is indicative of MCI and specific to certain time windows, frequency bands and brain regions. These results could represent two neurophysiological sides of MCI. Characterizing these opposing processes may contribute to the understanding of the disorder.
Rubber Hand Illusion survives Ventral Premotor area inhibition: A rTMS study.
Neuropsychologia, 2018

The sense of body ownership is a fundamental feature that refers to the ability to recognize our body as our own, allowing us to interact properly with the outside world. Usually, it is explored by means of the Rubber Hand Illusion (RHI) during which a dummy hand is incorporated in the mental representation of one's own body throughout a multisensory (visuo-tactile) integration mechanism. Particular attention has been paid to the neurofunctional counterparts of this mechanism highlighting the pivotal role of an occipito-parieto-frontal network involving the Ventral Premotor area (PMv). To date, the specific role of the PMv in generating the sense of ownership is still unknown. In this study, we aimed at exploring the role of PMv in generating and experiencing the RHI. Off-line repetitive Transcranial Magnetic Stimulation (rTMS) was applied to a group of 24 healthy participants whilst changes in proprioceptive judgment and self-reported illusion sensations were collected and analysed separately. The PMv was not directly implicated in generating the sense of ownership. Indeed, its inhibition affected the explicit detection of the visuo-tactile congruence without interfering with the illusion experience itself. We hypothesized that the conscious visuo-tactile congruence detection may be independent from the conscious illusion experience. Also, our results support the view that the RHI grounds on a complex interaction between bottom-up and top-down processes, as the visuo-tactile integration per se may be not sufficient to trigger the subjective illusion.
Development and initial testing of a tailored telephone intervention delivered by peers to prevent recurring opioid-overdoses (TTIP-PRO).
Health education research, 2016

Individuals with opioid use disorder experiencing a non-fatal opioid-overdose (OOD) are at heightened risk for future OODs; there are no interventions to facilitate treatment enrollment for these patients. Our goal was to develop and initially test the 'tailored telephone intervention delivered by peers to prevent recurring opioid-overdoses' (TTIP-PRO), a computer-facilitated, peer-delivered, individually tailored secondary prevention intervention designed to: (i) encourage patients to initiate medication-assisted treatment (MAT) and (ii) increase OOD knowledge. A pre-post-study assessed TTIP-PRO-content acceptability and software performance. Two Peer Interventionists, who were abstinent from illicit opioids, enrolled in MAT and had experience with OOD, were recruited from a MAT clinic. Recruitment letters were sent to patients treated for OOD in a hospital emergency department within the prior 8 months. Eight patients received TTIP-PRO and completed pre-/post-assessment. Peer Interventionists completed training within 4 h and reported high satisfaction with TTIP-PRO. There were no performance issues with the software. All participants rated TTIP-PRO as 'very helpful'. Participants' OOD knowledge increased significantly, with 69.9% correct responses pre-TTIP-PRO and 93.6% post-TTIP-PRO. Interest in receiving MAT, measured on a 10-point scale, increased from 8.1 to 9.5, but this change was not statistically significant. Further development and testing of TTIP-PRO appears warranted.
In vitro assessment of the agonist properties of the novel 5-HT1A receptor ligand, CUMI-101 (MMP), in rat brain tissue.
Nuclear medicine and biology, 2011

Development of agonist positron emission tomography (PET) radioligands for the 5-HT neurotransmitter system is an important target to enable the understanding of human 5-HT function in vivo. [(11)C]CUMI-101, proposed as the first 5-HT(1A) receptor agonist PET ligand, has been reported to behave as a potent 5-HT(1A) agonist in a cellular system stably expressing human recombinant 5-HT(1A) receptors. In this study, we investigate the agonist properties of CUMI-101 in rat brain tissue.
Impaired peripheral reaching and on-line corrections in patient DF: Optic ataxia with visual form agnosia.
Cortex; a journal devoted to the study of the nervous system and behavior, 2018

An influential model of vision suggests the presence of two visual streams within the brain: a dorsal occipito-parietal stream which mediates action and a ventral occipito-temporal stream which mediates perception. One of the cornerstones of this model is DF, a patient with visual form agnosia following bilateral ventral stream lesions. Despite her inability to identify and distinguish visual stimuli, DF can still use visual information to control her hand actions towards these stimuli. These observations have been widely interpreted as demonstrating a double dissociation from optic ataxia, a condition observed after bilateral dorsal stream damage in which patients are unable to act towards objects that they can recognize. In Experiment 1, we investigated how patient DF performed on the classical diagnostic task for optic ataxia, reaching in central and peripheral vision. We replicated recent findings that DF is remarkably inaccurate when reaching to peripheral targets, but not when reaching in free vision. In addition we present new evidence that her peripheral reaching errors follow the optic ataxia pattern increasing with target eccentricity and being biased towards fixation. In Experiments 2 and 3, for the first time we examined DF's on-line control of reaching using a double-step paradigm in fixation-controlled and free-vision versions of the task. DF was impaired when performing fast on-line corrections on all conditions tested, similarly to optic ataxia patients. Our findings question the long-standing assumption that DF's dorsal visual stream is functionally intact and that her on-line visuomotor control is spared. In contrast, in addition to visual form agnosia, DF also has visuomotor symptoms of optic ataxia which are most likely explained by bilateral damage to the superior parietal-occipital cortex (SPOC). We thus conclude that patient DF can no longer be considered as an appropriate single-case model for testing the neural basis of perception and action dissociations.
Transcranial static magnetic stimulation over the motor cortex can facilitate the contralateral cortical excitability in human.
Scientific reports, 2021

Transcranial static magnetic stimulation (tSMS) has been focused as a new non-invasive brain stimulation, which can suppress the human cortical excitability just below the magnet. However, the non-regional effects of tSMS via brain network have been rarely studied so far. We investigated whether tSMS over the left primary motor cortex (M1) can facilitate the right M1 in healthy subjects, based on the hypothesis that the functional suppression of M1 can cause the paradoxical functional facilitation of the contralateral M1 via the reduction of interhemispheric inhibition (IHI) between the bilateral M1. This study was double-blind crossover trial. We measured the corticospinal excitability in both M1 and IHI from the left to right M1 by recording motor evoked potentials from first dorsal interosseous muscles using single-pulse and paired-pulse transcranial magnetic stimulation before and after the tSMS intervention for 30 min. We found that the corticospinal excitability of the left M1 decreased, while that of the right M1 increased after tSMS. Moreover, the evaluation of IHI revealed the reduced inhibition from the left to the right M1. Our findings provide new insights on the mechanistic understanding of neuromodulatory effects of tSMS in human.
Vestibular processing during natural self-motion: implications for perception and action.
Nature reviews. Neuroscience, 2019

How the brain computes accurate estimates of our self-motion relative to the world and our orientation relative to gravity in order to ensure accurate perception and motor control is a fundamental neuroscientific question. Recent experiments have revealed that the vestibular system encodes this information during everyday activities using pathway-specific neural representations. Furthermore, new findings have established that vestibular signals are selectively combined with extravestibular information at the earliest stages of central vestibular processing in a manner that depends on the current behavioural goal. These findings have important implications for our understanding of the brain mechanisms that ensure accurate perception and behaviour during everyday activities and for our understanding of disorders of vestibular processing.
Optocardiography and Electrophysiology Studies of Ex Vivo Langendorff-perfused Hearts.
Journal of visualized experiments : JoVE, 2019

Small animal models are most commonly used in cardiovascular research due to the availability of genetically modified species and lower cost compared to larger animals. Yet, larger mammals are better suited for translational research questions related to normal cardiac physiology, pathophysiology, and preclinical testing of therapeutic agents. To overcome the technical barriers associated with employing a larger animal model in cardiac research, we describe an approach to measure physiological parameters in an isolated, Langendorff-perfused piglet heart. This approach combines two powerful experimental tools to evaluate the state of the heart: electrophysiology (EP) study and simultaneous optical mapping of transmembrane voltage and intracellular calcium using parameter sensitive dyes (RH237, Rhod2-AM). The described methodologies are well suited for translational studies investigating the cardiac conduction system, alterations in action potential morphology, calcium handling, excitation-contraction coupling and the incidence of cardiac alternans or arrhythmias.