Channelopathies and dendritic dysfunction in fragile X syndrome.

Channelopathies and dendritic dysfunction in fragile X syndrome. Brain Res Bull. 2014 Jan 23; Authors: Brager DH, Johnston D Abstract Dendritic spine abnormalities and the metabotropic glutamate receptor theory put the focus squarely on synapses and protein synthesis as the cellular locus of fragile X syndrome. Synapses however, are only partly responsible for information processing in neuronal networks. Neurotransmitter triggered excitatory postsynaptic potentials (EPSPs) are shaped and integrated by dendritic voltage-gated ion channels. These EPSPs, and in some cases the resultant dendritic spikes, are further modified by dendritic voltage-gated ion channels as they propagate to the soma. If the resultant somatic depolarization is large enough, action potential(s) will be triggered and propagate both orthodromically down the axon, where it may trigger neurotransmitter release, and antidromically back into the dendritic tree, where it can activate and modify dendritic voltage-gated and receptor activated ion channels. Several channelopathies, both soma-dendritic (L-type calcium channels, Slack potassium channels, h-channels, A-type potassium channels) and axo-somatic (BK channels and delayed rectifier potassium channels) were identified in the fmr1-/y mouse model of fragile X syndrome. Pathological function of these channels will strongly influence the excitability of individual neurons as well as overall network function. In this chapter we discuss the role...
Source: Brain Research Bulletin - Category: Neurology Authors: Tags: Brain Res Bull Source Type: research

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Publication date: August 2019Source: The Lancet Neurology, Volume 18, Issue 8Author(s): The Lancet Neurology
Source: The Lancet Neurology - Category: Neurology Source Type: research
Journal Name: Journal of Pediatric Endocrinology and Metabolism Issue: Ahead of print
Source: Journal of Pediatric Endocrinology and Metabolism - Category: Endocrinology Source Type: research
Publication date: Available online 2 July 2019Source: Pharmacological ResearchAuthor(s): Maria Rosaria Domenici, Antonella Ferrante, Alberto Martire, Valentina Chiodi, Rita Pepponi, Maria Teresa Tebano, Patrizia PopoliAbstractAdenosine A2A receptor (A2AR) is a G-protein coupled receptor that regulates several important functions in the central nervous system. Large amount of preclinical data suggests that the A2AR could represent a target for the development of new therapeutic strategies for different neuropsychiatric conditions. In this review we will recapitulate and discuss the most relevant studies on the role of A2ARs...
Source: Pharmacological Research - Category: Drugs & Pharmacology Source Type: research
AbstractThere are frequent studies undergoing related to the Fragile X syndrome caused due to the triplet CGG replicates on the X chromosome of Fragile X Mental Retardation 1 (FMR1) gene. Mutations of this chromosome can lead to Fragile X syndrome, rational disability, and other cognitive discrepancies. A novel approach based on Rajan Transform is proposed to analyze the spectral density of codons. The traditional transform like Fourier transform provides imaginary values whereas the Rajan Transform exhibits only the real values. The mutations there in the DNA are successfully distinguished by using the Rajan Transform whi...
Source: Journal of Medical Systems - Category: Information Technology Source Type: research
Abstract Fragile X Syndrome (FXS) is a leading genetic cause of autism and intellectual disabilities. The Fmr1 knockout (KO) mouse is a commonly studied pre-clinical model of FXS. Adult male Fmr1 KO mice produce fewer ultrasonic vocalizations (USVs) during mating, suggestive of abnormal social communication. Minocycline treatment for 2 months from birth alleviates a number of FXS phenotypes in mice, including USV call rate deficits. In the current study, we investigated if treatment initiated past the early developmental period would be effective, given that in many cases, individuals with FXS are treated during l...
Source: Behavioural Brain Research - Category: Neurology Authors: Tags: Behav Brain Res Source Type: research
Publication date: Available online 28 June 2019Source: Stem Cell ResearchAuthor(s): Subhajit Giri, Meera Purushottam, Biju Viswanath, Ravi S. MuddashettyAbstractMutations in FMR1 gene is the cause of Fragile X Syndrome (FXS) leading inherited cause of intellectual disability and autism spectrum disorders. FMR1 gene encodes Fragile X Mental Retardation Protein (FMRP) which is a RNA binding protein and play important role in synaptic plasticity and translational regulation in neurons. We have generated a homozygous FMR1 knockout (FMR1-KO) hESC line using CRISPR/Cas9 based genome editing. It created a homozygous 280 nucleotid...
Source: Stem Cell Research - Category: Stem Cells Source Type: research
Purpose of review Research on the pathophysiology of syndromic autism spectrum disorder (ASD) has contributed to the uncovering of mechanisms in nonsyndromic ASD. The current review aims to compare recent progress in therapeutics development for ASD with those for fragile X syndrome (FXS), the most frequent monogenic form of ASD. Recent findings Although candidates such as oxytocin, vasopressin, and cannabinoids are being tested as novel therapeutics, it remains difficult to focus on a specific molecular target of drug development for ASD core symptoms. As the pathophysiology of FXS has been well described as having a...
Source: Current Opinion in Neurology - Category: Neurology Tags: DEVELOPMENTAL DISORDERS: Edited by Doris A. Trauner Source Type: research
Conclusion This study contributes to scant knowledge of early communication phenotypes of infant ASIBs who do not meet criteria for ASD and infants with FXS. Results indicated that gesture function, not frequency, best discriminated at-risk infants from low-risk infants at 12 months of age. Findings have implications for the clinical evaluation and treatment of infants at high risk for ASD and communication disorders. PMID: 31251678 [PubMed - as supplied by publisher]
Source: Journal of speech, language, and hearing research : JSLHR - Category: Speech-Language Pathology Authors: Tags: J Speech Lang Hear Res Source Type: research
Abstract Estimates of the prevalence of speech and motor speech disorders in persons with complex neurodevelopmental disorders (CND) can inform research in the biobehavioural origins and treatment of CND. The goal of this research was to use measures and analytics in a diagnostic classification system to estimate the prevalence of speech and motor speech disorders in convenience samples of speakers with one of eight types of CND. Audio-recorded conversational speech samples from 346 participants with one of eight types of CND were obtained from a database of participants recruited for genetic and behavioural studi...
Source: Clinical Linguistics and Phonetics - Category: Speech-Language Pathology Authors: Tags: Clin Linguist Phon Source Type: research
Abstract Tandem microsatellite repeats are common throughout the human genome and intrinsically unstable, exhibiting expansions and contractions both somatically and across generations. Instability in a small subset of these repeats are currently linked to human disease, although recent findings suggest more disease-causing repeats await discovery. These nucleotide repeat expansion disorders (NREDs) primarily affect the nervous system and commonly lead to neurodegeneration through toxic protein gain-of-function, protein loss-of-function, and toxic RNA gain-of-function mechanisms. However, the lines between these c...
Source: Neurobiology of Disease - Category: Neurology Authors: Tags: Neurobiol Dis Source Type: research
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