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Genetic mosaicism, intrafamilial phenotypic heterogeneity, and molecular defects of a novel missense SLC6A1 mutation associated with epilepsy and ADHD.

Exp Neurol 2021 May 4:113723. Epub 2021 May 4.

Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, 37232, United States of America. Electronic address:

Background: Mutations in SLC6A1, encoding γ-aminobutyric acid (GABA) transporter 1 (GAT-1), have been recently associated with a spectrum of neurodevelopmental disorders ranging from variable epilepsy syndromes, intellectual disability (ID), autism and others. To date, most identified mutations are de novo. We here report a pedigree of two siblings associated with myoclonic astatic epilepsy, attention deficit hyperactivity disorder (ADHD), and ID. Read More

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Growing up after childhood cancer: maturity and life satisfaction in young adulthood.

Support Care Cancer 2021 May 7. Epub 2021 May 7.

Center for Biobehavioral Health, The Abigail Wexner Research Institute At Nationwide Children's Hospital, Columbus, OH, USA.

Purpose: Young individuals face a variety of developmental tasks as they mature into adulthood. For survivors of childhood cancer, growing up may be more difficult due to their illness and late effects from treatment. This study is the first to quantitatively examine perceptions of maturity and how these perceptions contribute to satisfaction with life among young adult survivors of childhood cancer. Read More

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Altered theta and beta oscillatory synchrony in a genetic mouse model of pathological anxiety.

FASEB J 2021 Jun;35(6):e21585

Department of Molecular Neurobiology, Max Planck Institute of Experimental Medicine, Göttingen, Germany.

While the neural circuits mediating normal, adaptive defensive behaviors have been extensively studied, substantially less is currently known about the network mechanisms by which aberrant, pathological anxiety is encoded in the brain. Here we investigate in mice how deletion of Neuroligin-2 (Nlgn2), an inhibitory synapse-specific adhesion protein that has been associated with pathological anxiety and other psychiatric disorders, alters the communication between key brain regions involved in mediating defensive behaviors. To this end, we performed multi-site simultaneous local field potential (LFP) recordings from the basolateral amygdala (BLA), centromedial amygdala (CeM), bed nucleus of the stria terminalis (BNST), prefrontal cortex (mPFC) and ventral hippocampus (vHPC) in an open field paradigm. Read More

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Transcriptomic Analysis Reveals an Altered Hcy Metabolism in the Stria Vascularis of the Pendred Syndrome Mouse Model.

Neural Plast 2021 17;2021:5585394. Epub 2021 Apr 17.

Department of Otolaryngology-Head and Neck Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.

Purpose: mice exhibit severer defects in the development of the cochlea and develop deafness, while the underlying mechanisms responsible for these effects remain unclear. Our study was to investigate the potential mechanism linking deficiency to hearing loss.

Materials And Methods: RNA sequencing was applied to analyze the differential gene expression of the stria vascularis (SV) from wildtype and mice. Read More

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Heschl's Gyrus Duplication Pattern in Individuals at Risk of Developing Psychosis and Patients With Schizophrenia.

Front Behav Neurosci 2021 20;15:647069. Epub 2021 Apr 20.

Department of Neuropsychiatry, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.

An increased prevalence of duplicated Heschl's gyrus (HG), which may reflect an early neurodevelopmental pathology, has been reported in schizophrenia (Sz). However, it currently remains unclear whether individuals at risk of psychosis exhibit similar brain morphological characteristics. This magnetic resonance imaging study investigated the distribution of HG gyrification patterns [i. Read More

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Vascular Senescence: A Potential Bridge Between Physiological Aging and Neurogenic Decline.

Front Neurosci 2021 20;15:666881. Epub 2021 Apr 20.

Departamento de Biología Celular, Biología Funcional y Antropología Física, Universitat de València, Valencia, Spain.

The adult mammalian brain contains distinct neurogenic niches harboring populations of neural stem cells (NSCs) with the capacity to sustain the generation of specific subtypes of neurons during the lifetime. However, their ability to produce new progeny declines with age. The microenvironment of these specialized niches provides multiple cellular and molecular signals that condition NSC behavior and potential. Read More

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DNA Hypermethylation Induced by L-Methionine Leads to Oligodendroglial and Myelin Deficits and Schizophrenia-Like Behaviors in Adolescent Mice.

Front Neurosci 2021 20;15:659853. Epub 2021 Apr 20.

Department of Histology and Embryology, Institute of Brain and Intelligence, Army Medical University (Third Military Medical University), Chongqing, China.

Increasing evidence has demonstrated that in addition to dysfunction of neuronal circuitry, oligodendroglial dysfunction and/or disruption of white matter integrity are found in the brains of patients with schizophrenia. DNA methylation, a well-established risk factor for schizophrenia, has been demonstrated to cause neuronal dysfunction; however, whether dysregulation of DNA methylation contributes to oligodendroglial/myelin deficits in the pathogenesis of schizophrenia remains unclear. In the present study, by using L-methionine-treated mice, we confirmed that mice with DNA hypermethylation exhibited an anxious phenotype, impaired sociability, and sensorimotor gating deficits. Read More

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Automated intracellular pharmacological electrophysiology for ligand-gated ionotropic receptor and pharmacology screening.

Mol Pharmacol 2021 May 6. Epub 2021 May 6.

George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, United States

Communication between neuronal cells, central to brain function, is performed by several classes of ligand-gated ionotropic receptors. The gold standard technique for measuring rapid receptor response to agonist is manual patch-clamp electrophysiology, capable of the highest temporal resolution of any current electrophysiology technique. We report an automated high-precision patch-clamp system which substantially improves the throughput of these time-consuming pharmacological experiments. Read More

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PET Imaging of Peripheral Benzodiazepine Receptor Standard Uptake Value Increases After Controlled Cortical Impact, a Rodent Model of Traumatic Brain Injury.

ASN Neuro 2021 Jan-Dec;13:17590914211014135

Department of Pediatric Surgery, University of Texas Medical School at Houston, Texas, United States.

Traumatic brain injury (TBI) is a chronic, life threatening injury for which few effective interventions are available. Evidence in animal models suggests un-checked immune activation may contribute to the pathophysiology. Changes in regional density of active brain microglia can be quantified in vivo with positron emission topography (PET) with the relatively selective radiotracer, peripheral benzodiazepine receptor 28 (11 C-PBR28). Read More

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Altered evoked low-frequency connectivity from SI to ACC following nerve injury in rats.

J Neural Eng 2021 May 6. Epub 2021 May 6.

Health science and technology, Aalborg University, Fredrik Bajers vej 7D-2, Aalborg, 9220, DENMARK.

Objective: Despite decades of research on central processing of pain, there are still several unanswered questions, in particular regarding the brain regions that may contribute to this alerting sensation. Since it is generally accepted that more than one cortical area is responsible for pain processing, there is an increasing focus on the interaction between areas known to be involved.

Approach: In this study, we aimed to investigate the bidirectional information flow from the primary somatosensory cortex (SI) to the anterior cingulate cortex (ACC) in an animal model of neuropathic pain. Read More

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Structural, Functional, and Metabolic Brain Differences as a Function of Gender Identity or Sexual Orientation: A Systematic Review of the Human Neuroimaging Literature.

Arch Sex Behav 2021 May 6. Epub 2021 May 6.

Division of Health Sciences, University of Edinburgh, Edinburgh, EH16 4SB, UK.

This review systematically explored structural, functional, and metabolic features of the cisgender brain compared with the transgender brain before hormonal treatment and the heterosexual brain compared to the homosexual brain from the analysis of the neuroimaging literature up to 2018, and identified and discussed subsequent studies published up to March 2021. Our main aim was to help identifying neuroradiological brain features that have been related to human sexuality to contribute to the understanding of the biological elements involved in gender identity and sexual orientation. We analyzed 39 studies on gender identity and 24 on sexual orientation. Read More

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Regulation of arsenic methylation: identification of the transcriptional region of the human AS3MT gene.

Cell Biol Toxicol 2021 May 6. Epub 2021 May 6.

Department of Cellular Biology and Pharmacology, Florida International University, Herbert Wertheim College of Medicine, Miami, FL, 33199, USA.

The human enzyme As(III) S-adenosylmethionine methyltransferase (AS3MT) catalyzes arsenic biotransformations and is considered to contribute to arsenic-related diseases. AS3MT is expressed in various tissues and cell types including liver, brain, adrenal gland, and peripheral blood mononuclear cells but not in human keratinocytes, urothelial, or brain microvascular endothelial cells. This indicates that AS3MT expression is regulated in a tissue/cell type-specific manner, but the mechanism of transcriptional regulation of expression of the AS3MT gene is not known. Read More

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Physical activity may contribute to brain health in multiple sclerosis: An MR volumetric and spectroscopy study.

J Neuroimaging 2021 May 6. Epub 2021 May 6.

Division for Performance and Health (Sports Medicine), Department of Sport and Sport Science, TU Dortmund University, Dortmund, Germany.

Background And Purpose: Physical activity may represent a disease-modifying therapy in persons with multiple sclerosis (pwMS). To date, there is limited research regarding mechanisms based on brain imaging for understanding the beneficial effects of physical activity in pwMS. This study examined the relationship between physical activity levels and thalamic and hippocampal volumes and brain metabolism in pwMS. Read More

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Obscure Involvement of MYC in Neurodegenerative Diseases and Neuronal Repair.

Mol Neurobiol 2021 May 5. Epub 2021 May 5.

Faculty of Special Education and Rehabilitation, University of Belgrade, Visokog Stevana 2, 11000, Belgrade, Serbia.

MYC is well known as a potent oncogene involved in regulating cell cycle and metabolism. Augmented MYC expression leads to cell cycle dysregulation, intense cell proliferation, and carcinogenesis. Surprisingly, its increased expression in neurons does not induce their proliferation, but leads to neuronal cell death and consequent development of a neurodegenerative phenotype. Read More

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Upregulation of Glutamatergic Receptors in Hippocampus and Locomotor Hyperactivity in Aged Spontaneous Hypertensive Rat.

Cell Mol Neurobiol 2021 May 5. Epub 2021 May 5.

Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University (KMU), Kaohsiung, Taiwan.

Epidemiologic studies have indicated that chronic hypertension may facilitate the progression of abnormal behavior, such as emotional irritability, hyperactivity, and attention impairment. However, the mechanism of how chronic hypertension affects the brain and neuronal function remains unclear. In this study, 58-week-old male spontaneously hypertensive rats (SHR) and age-matched Wistar-Kyoto (WKY) control rats were used. Read More

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Stress-Induced Neuron Remodeling Reveals Differential Interplay Between Neurexin and Environmental Factors in Caenorhabditis elegans.

Authors:
Michael P Hart

Genetics 2019 Dec;213(4):1415-1430

Department of Genetics, University of Pennsylvania, Philadelphia, Pennsylvania 19104.

Hart characterizes a novel interaction between genetics and environmental stress on experience-dependent neuron remodeling and plasticity in Caenorhabditis elegans, defining an interplay between different forms of adolescent stress and the autism-associated gene neurexin... Read More

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December 2019

Body Size and Tissue-Scaling Is Regulated by Motoneuron-Derived Activinß in Drosophila melanogaster.

Genetics 2019 Dec;213(4):1447-1464

Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, Minnesota 55455.

Correct scaling of body and organ size is crucial for proper development, and the survival of all organisms. Perturbations in circulating hormones, including insulins and steroids, are largely responsible for changing body size in response to both genetic and environmental factors. Such perturbations typically produce adults whose organs and appendages scale proportionately with final size. Read More

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December 2019

Stress-Induced Neuron Remodeling Reveals Differential Interplay Between Neurexin and Environmental Factors in Caenorhabditis elegans.

Authors:
Michael P Hart

Genetics 2019 Dec;213(4):1415-1430

Department of Genetics, University of Pennsylvania, Philadelphia, Pennsylvania 19104.

Hart characterizes a novel interaction between genetics and environmental stress on experience-dependent neuron remodeling and plasticity in Caenorhabditis elegans, defining an interplay between different forms of adolescent stress and the autism-associated gene neurexin... Read More

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December 2019

Body Size and Tissue-Scaling Is Regulated by Motoneuron-Derived Activinß in Drosophila melanogaster.

Genetics 2019 Dec;213(4):1447-1464

Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, Minnesota 55455.

Correct scaling of body and organ size is crucial for proper development, and the survival of all organisms. Perturbations in circulating hormones, including insulins and steroids, are largely responsible for changing body size in response to both genetic and environmental factors. Such perturbations typically produce adults whose organs and appendages scale proportionately with final size. Read More

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December 2019

Abnormal Function in Dentate Nuclei Precedes the Onset of Psychosis: A Resting-State fMRI Study in High-Risk Individuals.

Schizophr Bull 2021 May 6. Epub 2021 May 6.

Department of Psychology, Northeastern University, Boston, MA.

Objective: The cerebellum serves a wide range of functions and is suggested to be composed of discrete regions dedicated to unique functions. We recently developed a new parcellation of the dentate nuclei (DN), the major output nuclei of the cerebellum, which optimally divides the structure into 3 functional territories that contribute uniquely to default-mode, motor-salience, and visual processing networks as indexed by resting-state functional connectivity (RsFc). Here we test for the first time whether RsFc differences in the DN, precede the onset of psychosis in individuals at risk of developing schizophrenia. Read More

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Binge-Like Ethanol Drinking Increases , , and Gene Expression in the Ventral Tegmental Area of Adult Mice.

Neurosci Insights 2021 16;16:26331055211009850. Epub 2021 Apr 16.

Center for Alcohol Research in Epigenetics, Department of Psychiatry, University of Illinois at Chicago, Chicago, IL, USA.

Alcohol use disorder is associated with pathophysiological changes in the dopaminergic system. Orthodenticle homeobox 2 (OTX2) is a transcription factor important for the development of dopaminergic neurons residing in the ventral tegmental area (VTA), a critical region of the brain involved in drug reinforcement. Previous studies have demonstrated that ethanol exposure during embryonic development reduces mRNA levels in the central nervous system. Read More

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Tumor-derived exosomal circRNA_102481 contributes to EGFR-TKIs resistance via the miR-30a-5p/ROR1 axis in non-small cell lung cancer.

Aging (Albany NY) 2021 May 5;13. Epub 2021 May 5.

Department of Thoracic Surgery, The First Hospital of Jilin University, Chaoyang, Changchun, Jilin, China.

Exosomes are messengers for intercellular communication and signal transduction. Circular RNA (circRNA) abnormal expression and regulation are involved in the occurrence and development of a variety of tumors. In the present study, exosomes in the serum of five patients with non-small cell lung cancer (NSCLC) were isolated before and after EGFR-TKIs resistance, and the circRNA expression profile was screened using a circRNA microarray. Read More

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Improving outcomes for primary school children at risk of cerebral visual impairments (the CVI project): study protocol for the process evaluation of a feasibility cluster-randomised controlled trial.

BMJ Open 2021 May 5;11(5):e044856. Epub 2021 May 5.

Bristol Medical School, University of Bristol, Bristol, UK

Introduction: Brain-related visual impairments, also known as cerebral visual impairment (CVI), are related to damage or poor function in the vision-related areas of the brain. There is broad agreement that CVI is an appropriate term to describe visual impairments that are not accounted by disorders of the eye or optic nerve, but differences remain as to which impairments can be included in this term. The CVI project is a programme of work that includes the development of a complex intervention to share knowledge with teachers, so that they can make both targeted and universal changes to support children with CVI. Read More

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Neuroinflammation in Mood Disorders: Role of Regulatory Immune Cells.

Neuroimmunomodulation 2021 May 5:1-9. Epub 2021 May 5.

Institute of Education and Research, Santa Casa BH, Belo Horizonte, Brazil.

Mood disorders are associated with chronic low-grade systemic (sterile) inflammation, with increased plasma levels of pro-inflammatory mediators targeting all tissues including the brain. Importantly, pro-inflammatory cytokines (ex., tumor-necrosis factor alpha [TNF-α], interleukin [IL]-6) regulate mood behavior and cognition by influencing neurotransmitter levels, activating stress-responsive endocrine axes, among other effects. Read More

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Microglia provide structural resolution to injured dendrites after severe seizures.

Cell Rep 2021 May;35(5):109080

Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA; Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, NJ 08854, USA; Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA; Department of Immunology, Mayo Clinic, Rochester, MN 55905, USA. Electronic address:

Although an imbalance between neuronal excitation and inhibition underlies seizures, clinical approaches that target these mechanisms are insufficient in containing seizures in patients with epilepsy, raising the need for alternative approaches. Brain-resident microglia contribute to the development and stability of neuronal structure and functional networks that are perturbed during seizures. However, the extent of microglial contributions in response to seizures in vivo remain to be elucidated. Read More

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Rhesus monkeys as a translational model for late-onset Alzheimer's disease.

Aging Cell 2021 May 5:e13374. Epub 2021 May 5.

Division of Geriatrics, Department of Medicine, SMPH, Madison, WI, USA.

Age is a major risk factor for late-onset Alzheimer's disease (AD) but seldom features in laboratory models of the disease. Furthermore, heterogeneity in size and density of AD plaques observed in individuals are not recapitulated in transgenic mouse models, presenting an incomplete picture. We show that the amyloid plaque microenvironment is not equivalent between rodent and primate species, and that differences in the impact of AD pathology on local metabolism and inflammation might explain established differences in neurodegeneration and functional decline. Read More

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GSK3ß inhibitor CHIR 99021 modulates cerebral organoid development through dose-dependent regulation of apoptosis, proliferation, differentiation and migration.

PLoS One 2021 5;16(5):e0251173. Epub 2021 May 5.

Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America.

Cerebral organoids generated from human pluripotent stem cells (hiPSCs) are unique in their ability to recapitulate human-specific neurodevelopmental events. They are capable of modeling the human brain and its cell composition, including human-specific progenitor cell types; ordered laminar compartments; and both cell-specific transcriptional signatures and the broader telencephalic transcriptional landscape. The serine/threonine kinase, GSK3β, plays a critical role in neurodevelopment, controlling processes as varied as neurogenesis, morphological changes, polarization, and migration. Read More

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Propolis Extract Regulate microRNA Expression in Glioblastoma and Brain Cancer Stem Cells.

Anticancer Agents Med Chem 2021 May 3. Epub 2021 May 3.

Ege University, Faculty of Medicine, Department of Pediatrics, Izmir, Turkey.

Background: Grade IV gliomas are classified as glioblastoma (GBM), which is the most malignant brain cancer type. Various genetic and epigenetic mechanisms play a role in the initiation and progression of GBM. MicroRNAs (miRNAs) are small, non-coding RNA molecules that are the main epigenetic regulatory RNA class. Read More

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The contributions of the left hippocampus and bilateral inferior parietal lobule to form-meaning associative learning.

Psychophysiology 2021 May 5:e13834. Epub 2021 May 5.

Key Laboratory of Brain, Cognition and Education Sciences, Ministry of Education, Guangzhou, China.

Existing studies have identified crucial roles for the hippocampus and a distributed set of cortical regions (e.g., the inferior parietal cortex) in learning novel words. Read More

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