rudyvdbrink/CitationDatabase huggingface dataset:
A single episode of early-life status epilepticus impacts neonatal ultrasonic vocalization behavior in the Fmr1 knockout mouse.
Epilepsy & behavior : E&B, 2020

Fragile X syndrome (FXS) is a genetic disorder caused by a trinucleotide (CGG) expansion mutation in the Fmr1 gene located on the X chromosome. It is characterized by hyperactivity, increased anxiety, repetitive-stereotyped behaviors, and impaired language development. Many children diagnosed with FXS also experience seizures during their lifetime. However, the underlying etiology of the relationship between FXS and epilepsy is not fully understood. Ultrasonic vocalizations (UVs) are one tool that may be used to measure early behavioral changes in mouse pups. In the present study, neonatal UVs were analyzed as a measure of communicative behavior in a mouse model of FXS, both with and without early-life seizures (ELSs). On postnatal day (PD) 10, status epilepticus (SE) was induced via intraperitoneal injections of 0.5% kainic acid (2.0 mg/kg) in male Fmr1 knockout (KO) and wild-type (WT) mice. On PD 12, all pups were temporarily isolated from their dam and UVs were recorded. Significant alterations were found in both spectral and temporal measures across genotype and seizure groups. Early-life seizure experience resulted in a significant increase in the quantity of UVs only in WT animals (p < 0.05). We also found that while there was no difference between genotypes in the total number of vocalizations made, calls produced by Fmr1 KO mice were significantly shorter and had a higher peak frequency compared with WT mice. Overall, these findings support the use of vocalization behavior as an early phenotypic marker and highlight the importance of utilizing double-hit models to better understand comorbid disorders.
rKv1.2 overexpression in the central medial thalamic area decreases caffeine-induced arousal.
Genes, brain, and behavior, 2011

The voltage-gated potassium channel Kv1.2 belongs to the shaker-related family and has recently been implicated in the control of sleep profile on the basis of clinical and experimental evidence in rodents. To further investigate whether increasing Kv1.2 activity would promote sleep occurrence in rats, we developed an adeno-associated viral vector that induces overexpression of rat Kv1.2 protein. The viral vector was first evaluated in vitro for its ability to overexpress rat Kv1.2 protein and to produce functional currents in infected U2OS cells. Next, the adeno-associated Kv1.2 vector was injected stereotaxically into the central medial thalamic area of rats and overexpression of Kv1.2 was showed by in situ hybridization, ex vivo electrophysiology and immunohistochemistry. Finally, the functional effect of Kv1.2 overexpression on sleep facilitation was investigated using telemetry system under normal conditions and following administration of the arousing agent caffeine, during the light phase. While no differences in sleep profile were observed between the control and the treated animals under normal conditions, a decrease in the pro-arousal effect of caffeine was seen only in the animals injected with the adeno-associated virus-Kv1.2 vector. Overall, our data further support a role of the Kv1.2 channel in the control of sleep profile, particularly under conditions of sleep disturbance.
Design and Implementation of an fMRI Study Examining Thought Suppression in Young Women with, and At-risk, for Depression.
Journal of visualized experiments : JoVE, 2015

Ruminative brooding is associated with increased vulnerability to major depression. Individuals who regularly ruminate will often try to reduce the frequency of their negative thoughts by actively suppressing them. We aim to identify the neural correlates underlying thought suppression in at-risk and depressed individuals. Three groups of women were studied; a major depressive disorder group, an at-risk group (having a first degree relative with depression) and controls. Participants performed a mixed block-event fMRI paradigm involving thought suppression, free thought and motor control periods. Participants identified the re-emergence of "to-be-suppressed" thoughts ("popping" back into conscious awareness) with a button press. During thought suppression the control group showed the greatest activation of the dorsolateral prefrontal cortex, followed by the at-risk, then depressed group. During the re-emergence of intrusive thoughts compared to successful re-suppression of those thoughts, the control group showed the greatest activation of the anterior cingulate cortices, followed by the at-risk, then depressed group. At-risk participants displayed anomalies in the neural regulation of thought suppression resembling the dysregulation found in depressed individuals. The predictive value of these changes in the onset of depression remains to be determined.
Duplication of the bodily self: a perceptual illusion of dual full-body ownership and dual self-location.
Royal Society open science, 2020

Previous research has shown that it is possible to use multisensory stimulation to induce the perceptual illusion of owning supernumerary limbs, such as two right arms. However, it remains unclear whether the coherent feeling of owning a full-body may be duplicated in the same manner and whether such a dual full-body illusion could be used to split the unitary sense of self-location into two. Here, we examined whether healthy human participants can experience simultaneous ownership of two full-bodies, located either close in parallel or in two separate spatial locations. A previously described full-body illusion, based on visuo-tactile stimulation of an artificial body viewed from the first-person perspective (1PP) via head-mounted displays, was adapted to a dual-body setting and quantified in five experiments using questionnaires, a behavioural self-location task and threat-evoked skin conductance responses. The results of experiments 1-3 showed that synchronous visuo-tactile stimulation of two bodies viewed from the 1PP lying in parallel next to each other induced a significant illusion of dual full-body ownership. In experiment 4, we failed to find support for our working hypothesis that splitting the visual scene into two, so that each of the two illusory bodies was placed in distinct spatial environments, would lead to dual self-location. In a final exploratory experiment (no. 5), we found preliminary support for an illusion of dual self-location and dual body ownership by using dynamic changes between the 1PPs of two artificial bodies and/or a common third-person perspective in the ceiling of the testing room. These findings suggest that healthy people, under certain conditions of multisensory perceptual ambiguity, may experience dual body ownership and dual self-location. These findings suggest that the coherent sense of the bodily self located at a single place in space is the result of an active and dynamic perceptual integration process.
Regulated expression of transgenes in embryonic stem cell-derived neural cells.
Genesis (New York, N.Y. : 2000), 2011

Discovery and characterization of gene promoters, enhancers and repressor binding elements is an important research area in neuroscience. Here, the suitability of embryonic stem cells and their neural derivatives as a model system for this research is investigated. Three neural transgenic constructs (from the Mnx1, Fabp7, and tuba1a genes) that have been validated in transgenic mice were inserted into embryonic stem cells as stable transgenes. These transgenic embryonic stem cells were differentiated into neural cultures and the pattern of transgene expression across a series of inducing conditions determined. The pattern of expression matched that predicted from transgenic mouse experiments for each of the three transgenes. The results show that embryonic stem cells and their neural derivatives comprise a promising model for investigating the mechanisms that control cell- and temporal-specific neural gene transcription.
NLRP3 Inflammasomes in Parkinson's disease and their Regulation by Parkin.
Neuroscience, 2020

Chronic inflammation might correlate with the formation of α-synuclein oligomers, subsequently leading to dopaminergic (DA) neuronal death in Parkinson's disease (PD). As major components of chronic inflammation, NOD-like receptor protein 3 (NLRP3) inflammasomes play a crucial role in PD via caspase 1 activation, primarily induced by mitochondrial damage. NLRP3 binds to apoptosis-associated speck-like protein containing a CARD (PYCARD/ASC), and forms inflammasomes in the brain. Inflammasomes act as a platform for caspase 1 to induce interleukin 1 Beta (IL1β) maturation, leading to neuronal pyroptosis. Furthermore, alpha-synuclein, whose abnormal aggregation is the main pathogenesis of PD, also activates NLRP3 inflammasomes. Mutations to PRKN (encoding Parkin) are the most common cause of autosomal recessive familial and sporadic early-onset PD. Evidence has confirmed a relationship between Parkin and NLRP3 inflammasomes. In this review, we summarize the current understanding of NLRP3 inflammasomes and their role in PD progression, and discuss their regulation by Parkin.
Ultra-short antibiotic prophylaxis guided by preoperative microbiological nasal swabs in endoscopic endonasal skull base surgery.
Acta neurochirurgica, 2021

Endoscopic endonasal skull base surgery (EESBS) is a clean-contaminated procedure. Guidelines regarding the antibiotic prophylaxis in EESBS have not been developed yet, and today, there are no universally accepted protocols. In this article, we investigated the efficacy of our new ultra-short antibiotic prophylaxis protocol for EESBS guided by the cultural results of preoperative microbiological nasal swabs.
Supranuclear ophthalmoparesis and vacuolar degeneration of the cerebral white matter in amyotrophic lateral sclerosis: a clinicopathological study.
Amyotrophic lateral sclerosis : official publication of the World Federation of Neurology Research Group on Motor Neuron Diseases, 2012

Possible clinicopathological relationship between vacuolar degeneration of cerebral white matter and clinical manifestation, especially of supranuclear ophthalmoparesis, both infrequent in amyotrophic lateral sclerosis (ALS) patients, was tested. Of 104 ALS sequential series, cases with vacuolar degeneration of the cerebral white matter were selected to yield 14 cases pathologically surveyed in this study. Clinical features were retrospectively assessed in their clinical records. Microscopic examination clarified vacuolar changes with fibrous gliosis, infiltration of macrophages, axonal degeneration with segmental dilatation and partial loss of myelin on electron microscopy. This histological change was extended into the cerebral white matter just under the cortices but sometimes accentuated as restricted areas along the pyramidal tract and precentral regions. In a patient with the most extensive focal lesion, these white matter vacuolar changes were detected with magnetic resonance imaging. The clinical manifestations linked to this focal vacuolar degeneration were disturbance of vertical ocular movements and shorter duration of the illness, compared with patients without vacuolar degeneration. In conclusion, histological demonstration of characteristic vacuolar degeneration in the white matter of ALS and its focal accentuation along precentral-pyramidal tracts are mutually related and possibly linked to clinical manifestations such as supranuclear ophthalmoparesis, an exceptional but possible manifestation of ALS.
Altered Phosphorylation of Cytoskeleton Proteins in Peripheral Blood Mononuclear Cells Characterizes Chronic Antibody-Mediated Rejection in Kidney Transplantation.
International journal of molecular sciences, 2020

Chronic antibody-mediated rejection (CAMR) is the major cause of kidney transplant failure. The molecular mechanisms underlying this event are still poorly defined and this lack of knowledge deeply influences the potential therapeutic strategies. The aim of our study was to analyze the phosphoproteome of peripheral blood mononuclear cells (PBMCs), to identify cellular signaling networks differentially activated in CAMR. Phosphoproteins isolated from PBMCs of biopsy proven CAMR, kidney transplant recipients with normal graft function and histology and healthy immunocompetent individuals, have been investigated by proteomic analysis. Phosphoproteomic results were confirmed by Western blot and PBMCs' confocal microscopy analyses. Overall, 38 PBMCs samples were analyzed. A differential analysis of PBMCs' phosphoproteomes revealed an increase of lactotransferrin, actin-related protein 2 (ARPC2) and calgranulin-B in antibody-mediated rejection patients, compared to controls. Increased expression of phosphorylated ARPC2 and its correlation to F-actin filaments were confirmed in CAMR patients. Our results are the first evidence of altered cytoskeleton organization in circulating immune cells of CAMR patients. The increased expression of phosphorylated ARPC2 found in the PBMCs of our patients, and its association with derangement of F-actin filaments, might suggest that proteins regulating actin dynamics in immune cells could be involved in the mechanism of CAMR of kidney grafts.
Tactics: an open-source platform for planning, simulating and validating stereotactic surgery.
Computer assisted surgery (Abingdon, England), 2020

Frame-based stereotaxy is widely used for planning and implanting deep-brain electrodes. In 2013, as part of a clinical study on deep-brain stimulation for treatment-resistant depression, our group identified a need for software to simulate and plan stereotactic procedures. Shortcomings in extant commercial systems encouraged us to develop Tactics. Tactics is purpose-designed for frame-based stereotactic placement of electrodes. The workflow is far simpler than commercial systems. By simulating specific electrode placement, immediate in-context view of each electrode contact, and the cortical entry site are available within seconds. Post implantation, electrode placement is verified by linearly registering post-operative images. Tactics has been particularly helpful for invasive electroencephalography electrodes where as many as 20 electrodes are planned and placed within minutes. Currently, no commercial system has a workflow supporting the efficient placement of this many electrodes. Tactics includes a novel implementation of automated frame localization and a user-extensible mechanism for importing electrode specifications for visualization of individual electrode contacts. The system was systematically validated, through comparison against gold-standard techniques and quantitative analysis of targeting accuracy using a purpose-built imaging phantom mountable by a stereotactic frame. Internal to our research group, Tactics has been used to plan over 300 depth-electrode targets and trajectories in over 50 surgical cases, and to plan dozens of stereotactic biopsies. Source code and pre-built binaries for Tactics are public and open-source, enabling use and contribution by the extended community.
Human Stem Cell-Derived Neurons Repair Circuits and Restore Neural Function.
Cell stem cell, 2021

Although cell transplantation can rescue motor defects in Parkinson's disease (PD) models, whether and how grafts functionally repair damaged neural circuitry in the adult brain is not known. We transplanted hESC-derived midbrain dopamine (mDA) or cortical glutamate neurons into the substantia nigra or striatum of a mouse PD model and found extensive graft integration with host circuitry. Axonal pathfinding toward the dorsal striatum was determined by the identity of the grafted neurons, and anatomical presynaptic inputs were largely dependent on graft location, whereas inhibitory versus excitatory input was dictated by the identity of grafted neurons. hESC-derived mDA neurons display A9 characteristics and restore functionality of the reconstructed nigrostriatal circuit to mediate improvements in motor function. These results indicate similarity in cell-type-specific pre- and post-synaptic integration between transplant-reconstructed circuit and endogenous neural networks, highlighting the capacity of hPSC-derived neuron subtypes for specific circuit repair and functional restoration in the adult brain.
Hippocampal Cortactin Levels are Reduced Following Spatial Working Memory Formation, an Effect Blocked by Chronic Calpain Inhibition.
Brain sciences, 2015

The mechanism by which the hippocampus facilitates declarative memory formation appears to involve, among other things, restructuring of the actin cytoskeleton within neuronal dendrites. One protein involved in this process is cortactin, which is an important link between extracellular signaling and cytoskeletal reorganization. In this paper, we demonstrate that total hippocampal cortactin, as well as Y421-phosphorylated cortactin are transiently reduced following spatial working memory formation in the radial arm maze (RAM). Because cortactin is a substrate of the cysteine protease calpain, we also assessed the effect of chronic calpain inhibition on RAM performance and cortactin expression. Calpain inhibition impaired spatial working memory and blocked the reduction in hippocampal cortactin levels following RAM training. These findings add to a growing body of research implicating cortactin and calpain in hippocampus-dependent memory formation.
Beneficial effects of vitamin D on anxiety and depression-like behaviors induced by unpredictable chronic mild stress by suppression of brain oxidative stress and neuroinflammation in rats.
Naunyn-Schmiedeberg's archives of pharmacology, 2021

The objective of this study was to investigate the protective effects of vitamin D (Vit D) on anxiety and depression-like behaviors induced by unpredictable chronic mild stress and brain tissue oxidative damage criteria and neuroinflammation in rats. The rats were treated as follows: (1) control, (2) UCMS, (3-5) Vit D 100, 1000, and 10,000 iu + UCMS. Rats were subjected to UCMS for a total of 4 weeks. During week 4, they received seven training trials. The brains were then collected to examine inflammation and oxidative stress criteria. Pretreatment with Vit D enhanced performances of the rats in the elevated plus maze (EPM) and open field (OF) and forced swimming test (FST). UCMS also increased MDA and interleukin-6 (IL-6) levels while decreased CAT, SOD, and thiol. Vit D reversed the effects of UCMS. The results of the current research revealed that Vit D improved UCMS-induced anxiety and depression via decreasing brain oxidative stress and inhibiting neuroinflammation.
Subthreshold doses of guanosine plus ketamine elicit antidepressant-like effect in a mouse model of depression induced by corticosterone: Role of GR/NF-κB/IDO-1 signaling.
Neurochemistry international, 2020

Augmentative treatment is considered the best second-option when a first-choice drug has partial limitations, particularly by allowing antidepressant dose reduction. Considering that ketamine has significant knock-on effects, this study investigated the effects of a single coadministration with subthreshold doses of ketamine plus guanosine in a corticosterone (CORT)-induced animal model of depression and the role of anti-inflammatory and antioxidant pathways. CORT administration (20 mg/kg, p.o. for 21 days) increased the immobility time in the tail suspension test (TST) and the grooming latency in the splash test (SPT), as well as reduced the total time of grooming in the SPT. These behavioral alterations were accompanied by impaired hippocampal slices viability, elevated immunocontent of nuclear factor-kappa B (NF-κB) and indoleamine-2,3-dioxygenase 1 (IDO-1), and reduced immunocontent of glucocorticoids receptor (GR), glutamate transporter (GLT-1), nuclear factor-erythroid 2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) in the hippocampus. CORT also decreased the thioredoxin reductase activity in the hippocampus, while reduced the glutathione reductase activity and non-protein thiols levels in both hippocampus and prefrontal cortex. In addition, elevated content of malondialdehyde and protein carbonyl was also observed in the hippocampus and prefrontal cortex of CORT-treated mice. Of note, a single administration of ketamine (0.1 mg/kg, i.p.) plus guanosine (0.01 mg/kg, p.o.) attenuated the depressive-like behavior and hippocampal slices impairments induced by CORT. The behavioral response obtained by the combined administration of these drugs was paralleled by the reestablishment of the CORT-induced molecular alterations on hippocampal GR, NF-κB, IDO-1, and GLT-1 immunocontent. Moreover, CORT-induced alterations on the antioxidant enzyme activity and oxidative stress markers were partially restored by ketamine plus guanosine treatment. Taken together, these findings suggest that guanosine might potentiate the effects of ketamine on inflammatory and oxidative markers that are elevated in depression.
Cardioinhibition can be the unique manifestation of epilepsy-like syncope.
Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society, 2015

Sudden death and syncope remain frequently unexplained despite numerous investigations. Here, we report the case of a pacemaker-implanted patient who presented during video-polysomnography recording a complete atrioventricular block simultaneously with an electrical seizure. Remarkably, the patient was completely asymptomatic. He had a history of recurrent syncope previously diagnosed as convulsive vasovagal syncope with cardioinhibition. This observation challenges the current belief that epilepsy-like syncope is a partial complex seizure systematically characterized by a stereotypical clinical course and ending suddenly with syncope. Physicians should know that syncope, followed by jerking movements, of cardiac origin is frequent and often misdiagnosed as epilepsy. Conversely, and although this is a rare condition, they should also be aware of the possibility of epilepsy-like syncope, even in the absence of any other principle symptoms evocative of epilepsy.
The wicked in court: a neuroscientific primer.
Annals of the New York Academy of Sciences, 2013

The criminal cases of Anders Breivik, the Norwegian shooter, and Bernard Madoff, the fraudulent American financier, are used as prominent examples of the complexity that courts have to explore when judging the severity and responsibility of felonies performed by different types of psychopaths. I outline the brain circuits subserving morally charged decisions in ordinary citizens and in patients with gross lesions in the same areas, along with singularities in these brain systems that have been detected in psychopaths. These neural signatures, combined with thorough neuropsychological examination, will hopefully improve the diagnoses and prognoses of criminals with dangerous psychopathic traits. In this respect, the profiles of incarcerated members of gangs are used to exemplify and distinguish among typical niches and varieties of psychopathy within criminal organizations. A discussion follows, presenting the complexities of novel research that is increasing the sophistication of these challenging but key intersections between neuroscience and law.