rudyvdbrink/CitationDatabase huggingface dataset:
Characterization of rodent constitutively active estrogen receptor α variants and their constitutive transactivation mechanisms.
General and comparative endocrinology, 2017

Estrogen receptor α (ERα) mRNAs exhibit remarkable heterogeneity owing to complicated alternative splicing. Some encode C-terminally-truncated ERα proteins, which display ligand-independent transactivation or dominant-negative activity. We previously characterized C-terminally-truncated ERα mRNA variants with cryptic sequences in humans and mice, and demonstrated that helices in the ligand-binding domains (LBDs) of ERα variants contribute to ligand-independent transcriptional activity. However, existence of non-conventional coding exons and generation of constitutively active ERα variants have remained to be examined in rats. To comparatively analyze modular organization and splicing profiles of the ERα genes, the range of C-terminally-truncated ERα variants was explored in rats and mice using rapid amplification of cDNA ends and RT-PCR cloning. Furthermore, their functions were determined in transiently transfected cells using expression constructs and luciferase reporter assays. Multiple cryptic exons and C-terminally-truncated ERα variant mRNAs were identified in rats and mice. Naturally occurring and artificially truncated variants/constructs lacking helix 5 potentially exhibited gain-of-function in transfected cells. Although cryptic exons and splicing profiles were poorly conserved among humans, mice, and rats, constitutively active variants were generated from the ERα genes. Moreover, the primary mechanism of ligand-independent activation by C-terminally-truncated ERα variants is C-terminus to helix 5 deletion in the LBD. This comparative study documented the complexity of ERα genes, mRNAs, and proteins, and further determined the underlying structural basis of ligand-independent activation by C-terminally-truncated ERα variants.
Pragmatic influences on sentence integration: Evidence from eye movements.
Quarterly journal of experimental psychology (2006), 2019

To understand a discourse, readers must rapidly process semantic and syntactic information and extract the pragmatic information these sources imply. An important question concerns how this pragmatic information influences discourse processing in return. We address this issue in two eye movement experiments that investigate the influence of pragmatic inferences on the processing of inter-sentence integration. In Experiments 1a and 1b, participants read two-sentence discourses in Chinese in which the first sentence introduced an event and the second described its consequence, where the sentences were linked using either the causal connective "suoyi" (meaning "so" or "therefore") or not. The second sentence included a target word that was unmarked or marked using the focus particle "zhiyou" (meaning "only") in Experiment 1a or "shi" (equivalent to an
Disruption of auto-inhibition underlies conformational signaling of ASIC1a to induce neuronal necroptosis.
Nature communications, 2020

We reported previously that acid-sensing ion channel 1a (ASIC1a) mediates acidic neuronal necroptosis via recruiting receptor-interacting protein kinase 1 (RIPK1) to its C terminus (CT), independent of its ion-conducting function. Here we show that the N-terminus (NT) of ASIC1a interacts with its CT to form an auto-inhibition that prevents RIPK1 recruitment/activation under resting conditions. The interaction involves glutamate residues at distal NT and is disrupted by acidosis. Expression of mutant ASIC1a bearing truncation or glutamate-to-alanine substitutions at distal NT causes constitutive cell death. The NT-CT interaction is further disrupted by N-ethylmaleimide-sensitive fusion ATPase (NSF), which associates with ASIC1a-NT under acidosis, facilitating RIPK1 interaction with ASIC1a-CT. Importantly, a membrane-penetrating synthetic peptide representing the distal 20 ASIC1a NT residues, NT
Ethanol intake under social circumstances or alone in sprague-dawley rats: impact of age, sex, social activity, and social anxiety-like behavior.
Alcoholism, clinical and experimental research, 2015

In human adolescents, heavy drinking is often predicted by high sociability in males and high social anxiety in females. This study assessed the impact of baseline levels of social activity and social anxiety-like behavior in group-housed adolescent and adult male and female Sprague-Dawley rats on ethanol (EtOH) intake when drinking alone or in a social group.
Fingolimod (FTY720) is not protective in the subacute MPTP mouse model of Parkinson's disease and does not lead to a sustainable increase of brain-derived neurotrophic factor.
Journal of neurochemistry, 2018

Parkinson's disease (PD) is characterized by the loss of midbrain dopaminergic neurons and aggregates of α-synuclein termed Lewy bodies. Fingolimod (FTY720) is an agonist of sphingosine-1 phosphate receptors and an approved oral treatment for multiple sclerosis. Fingolimod elevates brain-derived neurotrophic factor (BDNF), an important neurotrophic factor for dopaminergic neurons. BDNF and fingolimod are beneficial in several animal models of PD. In order to validate the therapeutic potential of fingolimod for the treatment of PD, we tested its effect in the subacute MPTP mouse model of PD. MPTP or vehicle was applied i.p. in doses of 30 mg/kg MPTP on five consecutive days. In order to recapitulate the combination of dopamine loss and α-synuclein aggregates found in PD, MPTP was first administered in Thy1-A30P-α-synuclein transgenic mice. Fingolimod was administered i.p. at a dose of 0.1 mg/kg every second day. Nigrostriatal degeneration was assayed by stereologically counting the number of dopaminergic neurons in the substantia nigra pars compacta, by analysing the concentration of catecholamines and the density of dopaminergic fibres in the striatum. MPTP administration produced a robust nigrostriatal degeneration, comparable to previous studies. Unexpectedly, we found no difference between mice with and without fingolimod treatment, neither at baseline, nor at 14 or 90 days after MPTP. Also, we found no effect of fingolimod in the subacute MPTP mouse model when we used wildtype mice instead of α-synuclein transgenic mice, and no effect with an increased dose of 1 mg/kg fingolimod administered every day. In order to explain these findings, we analysed BDNF regulation by fingolimod. We did find an increase of BDNF protein after a single injection of fingolimod 0.1 or 1.0 mg/kg, but not after multiple injections, indicating that the BDNF response to fingolimod is unsustainable over time. Taken together we did not observe a neuroprotective effect of fingolimod in the subacute MPTP mouse model of PD. We discuss possible explanations for this discrepancy with previous findings and conclude fingolimod might be beneficial for the nonmotor symptoms of PD. OPEN SCIENCE BADGES: This article has received a badge for *Open Materials* and *Open Data* because it provided all relevant information to reproduce the study in the manuscript and because it made the data publicly available. The data can be accessed at https://osf.io/6xgfn/. The complete Open Science Disclosure form for this article can be found at the end of the article. More information about the Open Practices badges can be found at https://cos.io/our-services/open-science-badges/.
Sensory coding mechanisms revealed by optical tagging of physiologically defined neuronal types.
Science (New York, N.Y.), 2019

Neural circuit analysis relies on having molecular markers for specific cell types. However, for a cell type identified only by its circuit function, the process of identifying markers remains laborious. We developed physiological optical tagging sequencing (PhOTseq), a technique for tagging and expression profiling of cells on the basis of their functional properties. PhOTseq was capable of selecting rare cell types and enriching them by nearly 100-fold. We applied PhOTseq to the challenge of mapping receptor-ligand pairings among pheromone-sensing neurons in mice. Together with in vivo ectopic expression of vomeronasal chemoreceptors, PhOTseq identified the complete combinatorial receptor code for a specific set of ligands.
What "works" in working memory? Separate systems for selection and updating of critical information.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2009

Cognition depends critically on working memory, the active representation of a limited number of items over short periods of time. In addition to the maintenance of information during the course of cognitive processing, many tasks require that some of the items in working memory become transiently more important than others. Based on cognitive models of working memory, we hypothesized two complementary essential cognitive operations to achieve this: a selection operation that retrieves the most relevant item, and an updating operation that changes the focus of attention onto it. Using functional magnetic resonance imaging, high-resolution oculometry, and behavioral analysis, we demonstrate that these two operations are functionally and neuroanatomically dissociated. Updating the attentional focus elicited transient activation in the caudal superior frontal sulcus and posterior parietal cortex. In contrast, increasing demands on selection selectively modulated activation in rostral superior frontal sulcus and posterior cingulate/precuneus. We conclude that prioritizing one memory item over others invokes independent mechanisms of mnemonic retrieval and attentional focusing, each with its distinct neuroanatomical basis within frontal and parietal regions. These support the developing understanding of working memory as emerging from the interaction between memory and attentional systems.
Bilateral postsynaptic actions of pyramidal tract and reticulospinal neurons on feline erector spinae motoneurons.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2010

Trunk muscles are important for postural adjustments associated with voluntary movements but little has been done to analyze mechanisms of supraspinal control of these muscles at a cellular level. The present study therefore aimed to investigate the input from pyramidal tract (PT) neurons to motoneurons of the musculus longissimus lumborum of the erector spinae and to analyze to what extent it is relayed by reticulospinal (RS) neurons. Intracellular records from motoneurons were used to evaluate effects of electrical stimulation of medullary pyramids and of axons of RS neurons descending in the medial longitudinal fasciculus (MLF). The results revealed that similar synaptic actions were evoked from the ipsilateral and contralateral PTs, including disynaptic and trisynaptic EPSPs and trisynaptic IPSPs. Stimulation of the MLF-evoked monosynaptic and disynaptic EPSPs and disynaptic or trisynaptic IPSPs in the same motoneurons. All short-latency PSPs of PT origin were abolished by transection of the MLF, while they remained after transection of PT fibers at a spinal level. Hence, RS neurons might serve as the main relay neurons of the most direct PT actions on musculus (m.) longissimus. However, longer-latency IPSPs remaining after MLF or PT spinal lesions and after ipsilateral or contralateral hemisection of spinal cord indicate that PT actions are also mediated by ipsilaterally and/or contralaterally located spinal interneurons. The bilateral effects of PT stimulation thereby provide an explanation why trunk movements after unilateral injuries of PT neurons (e.g., stroke) are impaired to a lesser degree than movements of the extremities.
Role of rodent secondary motor cortex in value-based action selection.
Nature neuroscience, 2011

Despite widespread neural activity related to reward values, signals related to upcoming choice have not been clearly identified in the rodent brain. Here we examined neuronal activity in the lateral (AGl) and medial (AGm) agranular cortex, corresponding to the primary and secondary motor cortex, respectively, in rats performing a dynamic foraging task. Choice signals, before behavioral manifestation of the rat's choice, arose in the AGm earlier than in any other areas of the rat brain previously studied under free-choice conditions. The AGm also conveyed neural signals for decision value and chosen value. By contrast, upcoming choice signals arose later, and value signals were weaker, in the AGl. We also found that AGm lesions made the rats' choices less dependent on dynamically updated values. These results suggest that rodent secondary motor cortex might be uniquely involved in both representing and reading out value signals for flexible action selection.
18FDG-microPET and MR DTI findings in Tor1a+/- heterozygous knock-out mice.
Neurobiology of disease, 2015

TorsinA is an important protein in brain development, and plays a role in the regulation of neurite outgrowth and synaptic function. Patients with the most common form of genetic dystonia carry a mutation (DYT1) in one copy of the Tor1a gene, a 3-bp deletion, causing removal of a single glutamic acid from torsinA. Previous imaging studies have shown that abnormal cerebellar metabolism and damaged cerebello-thalamo-cortical pathway contribute to the pathophysiology of DYT1 dystonia. However, how a mutation in one copy of the Tor1a gene causes these abnormalities is not known. We studied Tor1a heterozygous knock-out mice in vivo with FDG-PET and ex vivo with diffusion tensor imaging. We found metabolic abnormalities in cerebellum, caudate-putamen, globus pallidus, sensorimotor cortex and subthalamic nucleus. We also found that FA was increased in caudate-putamen, sensorimotor cortex and brainstem. We compared our findings with a previous imaging study of the Tor1a knock-in mice. Our study suggested that having only one normal copy of Tor1a gene may be responsible for the metabolic abnormalities observed; having a copy of mutant Tor1a, on the other hand, may be responsible for white matter pathway damages seen in DYT1 dystonia subjects.
Hippocampal Sclerosis in Frontotemporal Dementia: When Vascular Pathology Meets Neurodegeneration.
Journal of neuropathology and experimental neurology, 2021

Hippocampal sclerosis (HS) is a common neuropathological finding and has been associated with advanced age, TDP-43 proteinopathy, and cerebrovascular pathology. We analyzed neuropathological data of an autopsy cohort of early-onset frontotemporal dementia patients. The study aimed to determine whether in this cohort HS was related to TDP-43 proteinopathy and whether additional factors could be identified. We examined the relationship between HS, proteinopathies in frontotemporal cortices and hippocampus, Alzheimer disease, cerebrovascular changes, and age. We confirmed a strong association between HS and hippocampal TDP-43, whereas there was a weaker association between HS and frontotemporal lobar degeneration with TDP-43 pathology (FTLD-TDP). Nearly all of the FTLD-TDP cases had TDP-43 pathology in the hippocampus. HS was present in all FTLD-TDP type D cases, in 50% of the FTLD-TDP A cohort and in 6% of the FTLD-TDP B cohort. Our data also showed a significant association between HS and vascular changes. We reviewed the literature on HS and discuss possible pathophysiological mechanisms between TDP-43 pathology, cerebrovascular disease, and HS. Additionally, we introduced a quantitative neuronal cell count in CA1 to objectify the semiquantitative visual appreciation of HS.
An Open Study of Sulforaphane-rich Broccoli Sprout Extract in Patients with Schizophrenia.
Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology, 2015

Schizophrenia is a mental disorder characterized by severe cognitive impairment. Accumulating evidence suggests a role for oxidative stress in the pathophysiology of schizophrenia. Sulforaphane (SFN) extracted from broccoli sprout is an agent with potent anti-oxidant and anti-inflammatory activity. In this study, we attempted to evaluate the effect of SFN on cognitive impairment in medicated patients with schizophrenia.
The integrated ultradian organization of behavior and physiology in mice and the contribution of orexin to the ultradian patterning.
Neuroscience, 2016

Our series of rat experiments have shown that locomotor activity, arousal level, body and brown adipose tissue temperatures, heart rate and arterial pressure increase episodically in an integrated manner approximately every 100min (ultradian manner). Although it has been proposed that the integrated ultradian pattern is a fundamental biological rhythm across species, there are no reports of the integrated ultradian pattern in species other than rats. The aim of the present study was to establish a mouse model using simultaneous recording of locomotor activity, eating behavior, body temperature, heart rate and arousal in order to determine whether their behavior and physiology are organized in an ultradian manner in normal (wild-type) mice. We also incorporated the same recording in prepro-orexin knockout (ORX-KO) mice to reveal the role of orexin in the brain mechanisms underlying ultradian patterning. The orexin system is one of the key conductors required for coordinating autonomic functions and behaviors, and thus may contribute to ultradian patterning. In wild-type mice, locomotor activity, arousal level, body temperature and heart rate increased episodically every 93±18min (n=8) during 24h. Eating was integrated into the ultradian pattern, commencing 23±4min (n=8) after the onset of an electroencephalogram (EEG) ultradian episode. The integrated ultradian pattern in wild-type mice is very similar to that observed in rats. In ORX-KO mice, the ultradian episodic changes in locomotor activity, EEG arousal indices and body temperature were significantly attenuated, but the ultradian patterning was preserved. Our findings support the view that the ultradian pattern is common across species. The present results also suggest that orexin contributes to driving ultradian episodic changes, however, this neuropeptide is not essential for the generation of the ultradian pattern.
Repetition probability does not affect fMRI repetition suppression for objects.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2013

Previously several functional magnetic resonance imaging (fMRI) studies point toward the role of perceptual expectations in determining adaptation or repetition suppression (RS) in humans. These studies showed that the probability of repetitions of faces within a block influences the magnitude of adaptation in face-related areas of the human brain (Summerfield et al., 2008). However, a current macaque single-cell/local field potential (LFP) recording study using objects as stimuli found no evidence for the modulation of the neural response by the repetition probability in the inferior temporal cortex (Kaliukhovich and Vogels, 2010). Here we examined whether stimulus repetition probability affects fMRI repetition suppression for nonface object stimuli in the human brain. Subjects were exposed to either two identical [repetition trials (RTs)] or two different [alternation trials (ATs)] object stimuli. Both types of trials were presented blocks consisting of either 75% [repetition blocks (RBs)] or 25% [alternation blocks (ABs)] of RTs. We found strong RS, i.e., a lower signal for RTs compared to ATs, in the object sensitive lateral occipital cortex as well as in the face-sensitive occipital and fusiform face areas. More importantly, however, there was no significant difference in the magnitude of RS between RBs and ABs in each of the areas. This is in agreement with the previous monkey single-unit/LFP findings and suggests that RS in the case of nonface visual objects is not modulated by the repetition probability in humans. Our results imply that perceptual expectation effects vary for different visual stimulus categories.
What are we measuring when we test strain differences in anxiety in mice?
Behavior genetics, 2013

We examined measures of locomotor and anxiety-like behavior in male and female mice of 15 inbred strains on the elevated-plus maze, light/dark transition box and open field. Strain differences were found on all measures of locomotor activity and anxiety. Strain means for measures of locomotor activity on the three apparatus were significantly correlated, but strain means for commonly used measures of anxiety were not correlated. Principal component analysis revealed a common locomotor activity factor, which accounted for 28.6 % of the variance, but no common anxiety factor. Species-typical behaviors (defecations, stretch-attend postures, grooming) accounted for smaller proportions (<11 %) of the variance. These results plus comparisons with previously published data suggest that the elevated-plus maze, light/dark box and open field measure different facets of anxiety, and that the reliability of genetic differences on anxiety is highly dependent on apparatus, procedural variables and laboratory factors. Locomotor activity, however, is a stable trait that differs across strains and is reliably measured in different apparatus and laboratories. We conclude that anxiety traits of inbred mouse strains are best reflected by species-typical behaviors in each apparatus. These results suggest that new ways of measuring trait anxiety are required in order to determine the neural and genetic correlates of anxiety-like behaviour in mice.
SARS-CoV-2 mediated neuroinflammation and the impact of COVID-19 in neurological disorders.
Cytokine & growth factor reviews, 2021

SARS-CoV-2 is a novel coronavirus that severely affects the respiratory system, is the cause of the COVID-19 pandemic, and is projected to result in the deaths of 2 million people worldwide. Recent reports suggest that SARS-CoV-2 also affects the central nervous system along with other organs. COVID-19-associated complications are observed in older people with underlying neurological conditions like stroke, Alzheimer's disease, and Parkinson's disease. Hence, we discuss SARS-CoV-2 viral replication and its inflammation-mediated infection. This review also focuses on COVID-19 associated neurological complications in individuals with those complications as well as other groups of people. Finally, we also briefly discuss the current therapies available to treat patients, as well as ongoing available treatments and vaccines for effective cures with a special focus on the therapeutic potential of a small 5 amino acid peptide (PHSCN), ATN-161, that inhibits SARS-CoV-2 spike protein binding to both integrin α5β1 and α5β1/hACE2.
Effect of transcutaneous electrical stimulation on nociception and edema induced by peripheral serotonin.
The International journal of neuroscience, 2013

Transcutaneous electrical nerve stimulation (TENS) is defined as the application of an electrical current to the skin through surface electrodes for pain relief. Various theories have been proposed in order to explain the analgesic mechanism of TENS. Recent studies have demonstrated that part of this analgesia is mediated through neurotransmitters acting at peripheral sites. The aim of this study was to investigate the effects of low frequency (LF: 10 HZ) TENS and high frequency (HF: 130 HZ) TENS on hyperalgesia and edema when applied before the serotonin (5-HT) administered into the rat paw. LF and HF TENS were applied to the right paw for 20 min, and 5-HT was administered immediately after TENS. The Hargreaves method was used to measure nociception, while the hydroplethysmometer (Ugo Basile®) was used to measure edema. Neither HF nor LF TENS inhibited 5-HT-induced edema. However, LF TENS, but not HF TENS, completely reduced 5-HT-induced hyperalgesia. Pre-treatment of the paw with naltrexone, prior to application of TENS, (Nx: 50 μg; I.pl.) showed a complete blockade of the analgesic effect induced by low frequency TENS. Thus, our results confirmed the lack of an anti-inflammatory effect through the use of TENS as well as the participation of peripheral endogenous opioid receptors in LF TENS analgesia in addition to its central action.