Molecular control of neurotransmitter linked to autism described

New research examines the role of KCC2, a transporter responsible for the discharge of chloride in cells, in developing disorders such as epilepsy and autism.
Source: Yale Science and Health News - Category: Universities & Medical Training Source Type: news

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hoj E Abstract The gamma-1 isoform of casein kinase 1, the protein encoded by CSNK1G1, is involved in the growth and morphogenesis of cells. This protein is expressed ubiquitously among many tissue types, including the brain, where it regulates the phosphorylation of NMDA receptors and plays a role in synaptic transmission. One prior individual with a de novo variant in CSNK1G presenting with severe developmental delay and early-onset epilepsy has been reported. Here we report an updated clinical history of this previously published case, as well as four additional individuals with de novo variants in CSNK1G1 iden...
Source: Clinical Genetics - Category: Genetics & Stem Cells Authors: Tags: Clin Genet Source Type: research
Abstract Posttranscriptional gene expression including splicing, RNA transport, translation and RNA decay provides an important regulatory layer in many if not all molecular pathways. Research in the last decades has positioned RNA-binding proteins (RBPs) right into the center of posttranscriptional gene regulation. We therefore propose interdependent networks of RBPs to regulate complex pathways within the central nervous system (CNS). These are involved in multiple aspects of neuronal formation and functioning including higher cognition. Therefore, it is not sufficient to unravel the individual contribution of a...
Source: Physiological Reviews - Category: Physiology Authors: Tags: Physiol Rev Source Type: research
Abstract Although COVID-19 is predominantly a respiratory disease, it is known to affect multiple organ systems. In this article, we highlight the impact of SARS-CoV-2 (the coronavirus causing COVID-19) on the central nervous system as there is an urgent need to understand the longitudinal impacts of COVID-19 on brain function, behaviour and cognition. Furthermore, we address the possibility of intergenerational impacts of COVID-19 on the brain, potentially via both maternal and paternal routes. Evidence from preclinical models of earlier coronaviruses has shown direct viral infiltration across the blood-brain bar...
Source: The Australian and New Zealand Journal of Psychiatry - Category: Psychiatry Authors: Tags: Aust N Z J Psychiatry Source Type: research
Abstract Copy number variations (CNVs) of the human 16p11.2 genetic locus are associated with a range of neurodevelopmental disorders, including autism spectrum disorder, intellectual disability, and epilepsy. In this review, we delineate genetic information and diverse phenotypes in individuals with 16p11.2 CNVs, and synthesize preclinical findings from transgenic mouse models of 16p11.2 CNVs. Mice with 16p11.2 deletions or duplications recapitulate many core behavioral phenotypes, including social and cognitive deficits, and exhibit altered synaptic function across various brain areas. Mechanisms of transcriptio...
Source: Trends in Neurosciences - Category: Neuroscience Authors: Tags: Trends Neurosci Source Type: research
Contributors : Anna N Rubin ; Kenneth J Lim ; Susan Lindtner ; John L RubensteinSeries Type : Genome binding/occupancy profiling by high throughput sequencingOrganism : Mus musculusCortical interneuron (CIN) dysfunction is thought to play a major role in neuropsychiatric conditions like epilepsy, schizophrenia and autism. It is therefore essential to understand how the development, physiology and functions of CINs influence cortical circuit activity and behavior in model organisms such as mice and primates. We sought to discover gene regulatory enhancer elements (REs) that can be used in AAV viral vectors to drive expressi...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Genome binding/occupancy profiling by high throughput sequencing Mus musculus Source Type: research
ConclusionThis case report provides evidence that a lower than previously reported dose of a phytocannabinoid in the form of a cannabidiol-based extract may be capable of aiding in autism spectrum disorder-related behavioral symptoms, core social communication abilities, and comorbid anxiety, sleep difficulties, and weight control. Further research is needed to elucidate the clinical role and underlying biological mechanisms of action of cannabidiol-based extract in patients with autism spectrum disorder.
Source: Journal of Medical Case Reports - Category: General Medicine Source Type: research
CONCLUSIONS.—: Because the death of autistic individuals is often because of an accident, drowning, suicide, or sudden unexpected death in epilepsy, they often are seen in a Medical Examiner's or Coroner's office. Yet, autism is rarely considered when evaluating the cause of death. Advances in our understanding of chronic traumatic encephalopathy have occurred because medical examiners and neuropathologists questioned whether a pathologic change might exist in individuals who played contact sports and later developed severe behavioral problems. This article highlights the potential for equally significant breakthroug...
Source: Archives of Pathology and Laboratory Medicine - Category: Laboratory Medicine Authors: Tags: Arch Pathol Lab Med Source Type: research
Tuberous sclerosis complex (TSC) represents the prototypic monogenic disorder of the mammalian target of rapamycin (mTOR) pathway dysregulation. It provides the rational mechanistic basis of a direct link between gene mutation and brain pathology (structural and functional abnormalities) associated with a complex clinical phenotype including epilepsy, autism, and intellectual disability. So far, research conducted in TSC has been largely neuron-oriented. However, the neuropathological hallmarks of TSC and other malformations of cortical development also include major morphological and functional changes in glial cells invo...
Source: Frontiers in Neurology - Category: Neurology Source Type: research
Conclusion This variation in clinical phenotype renders correct clinical interpretation and diagnosis challenging. Therefore, it is critical to elucidate the variable clinical phenotypes of rare CNVs, including 16p11.2 deletions, to help guide clinical monitoring and counselling of patients and families.
Source: Psychiatric Genetics - Category: Genetics & Stem Cells Tags: Original Articles Source Type: research
Valproic acid (VPA) is a widely used anti-epileptic drug (AED) of demonstrated efficacy [1,2]. However, since the 1980s, numerous published studies have highlighted the association between intrauterine exposure to VPA and the risk of a major congenital malformation (MCM) and neurodevelopmental problems. The risk of MCMs has been estimated at around 11%, with it increasing to 25% for doses above 1450  mg/day [3]. In children with intrauterine exposure to VPA, there is also evidence of an 8-10 point reduction in intelligence quotient (IQ) [4,5] and a 6-15% increase in the risk of developing an autism spectrum disorder (ASD) [6,7].
Source: Seizure: European Journal of Epilepsy - Category: Neurology Authors: Source Type: research
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