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Neural Hyperactivity Is a Core Pathophysiological Change Induced by Deletion of a High Autism Risk Gene Ash1L in the Mouse Brain

ASH1L is one of the highest risk genes associated with autism spectrum disorder (ASD) and intellectual disability (ID). Our recent studies demonstrate that loss of Ash1l in the mouse brain is sufficient to induce ASD/ID-like behavioral and cognitive deficits, suggesting that disruptive ASH1L mutatio...

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Autores principales: Gao, Yuen, Aljazi, Mohammad B., He, Jin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9016273/
https://www.ncbi.nlm.nih.gov/pubmed/35449559
http://dx.doi.org/10.3389/fnbeh.2022.873466
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author Gao, Yuen
Aljazi, Mohammad B.
He, Jin
author_facet Gao, Yuen
Aljazi, Mohammad B.
He, Jin
author_sort Gao, Yuen
collection PubMed
description ASH1L is one of the highest risk genes associated with autism spectrum disorder (ASD) and intellectual disability (ID). Our recent studies demonstrate that loss of Ash1l in the mouse brain is sufficient to induce ASD/ID-like behavioral and cognitive deficits, suggesting that disruptive ASH1L mutations are likely to have a positive correlation with ASD/ID genesis. However, the core pathophysiological changes in the Ash1l-deficient brain remain largely unknown. Here we show that loss of Ash1l in the mouse brain causes locomotor hyperactivity, high metabolic activity, and hyperactivity-related disturbed sleep and lipid metabolic changes. In addition, the mutant mice display lower thresholds for the convulsant reagent-induced epilepsy and increased neuronal activities in multiple brain regions. Thus, our current study reveals that neural hyperactivity is a core pathophysiological change in the Ash1l-deficient mouse brain, which may function as a brain-level mechanism leading to the Ash1l-deletion-induced brain functional abnormalities and autistic-like behavioral deficits.
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spelling pubmed-90162732022-04-20 Neural Hyperactivity Is a Core Pathophysiological Change Induced by Deletion of a High Autism Risk Gene Ash1L in the Mouse Brain Gao, Yuen Aljazi, Mohammad B. He, Jin Front Behav Neurosci Behavioral Neuroscience ASH1L is one of the highest risk genes associated with autism spectrum disorder (ASD) and intellectual disability (ID). Our recent studies demonstrate that loss of Ash1l in the mouse brain is sufficient to induce ASD/ID-like behavioral and cognitive deficits, suggesting that disruptive ASH1L mutations are likely to have a positive correlation with ASD/ID genesis. However, the core pathophysiological changes in the Ash1l-deficient brain remain largely unknown. Here we show that loss of Ash1l in the mouse brain causes locomotor hyperactivity, high metabolic activity, and hyperactivity-related disturbed sleep and lipid metabolic changes. In addition, the mutant mice display lower thresholds for the convulsant reagent-induced epilepsy and increased neuronal activities in multiple brain regions. Thus, our current study reveals that neural hyperactivity is a core pathophysiological change in the Ash1l-deficient mouse brain, which may function as a brain-level mechanism leading to the Ash1l-deletion-induced brain functional abnormalities and autistic-like behavioral deficits. Frontiers Media S.A. 2022-04-05 /pmc/articles/PMC9016273/ /pubmed/35449559 http://dx.doi.org/10.3389/fnbeh.2022.873466 Text en Copyright © 2022 Gao, Aljazi and He. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Behavioral Neuroscience
Gao, Yuen
Aljazi, Mohammad B.
He, Jin
Neural Hyperactivity Is a Core Pathophysiological Change Induced by Deletion of a High Autism Risk Gene Ash1L in the Mouse Brain
title Neural Hyperactivity Is a Core Pathophysiological Change Induced by Deletion of a High Autism Risk Gene Ash1L in the Mouse Brain
title_full Neural Hyperactivity Is a Core Pathophysiological Change Induced by Deletion of a High Autism Risk Gene Ash1L in the Mouse Brain
title_fullStr Neural Hyperactivity Is a Core Pathophysiological Change Induced by Deletion of a High Autism Risk Gene Ash1L in the Mouse Brain
title_full_unstemmed Neural Hyperactivity Is a Core Pathophysiological Change Induced by Deletion of a High Autism Risk Gene Ash1L in the Mouse Brain
title_short Neural Hyperactivity Is a Core Pathophysiological Change Induced by Deletion of a High Autism Risk Gene Ash1L in the Mouse Brain
title_sort neural hyperactivity is a core pathophysiological change induced by deletion of a high autism risk gene ash1l in the mouse brain
topic Behavioral Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9016273/
https://www.ncbi.nlm.nih.gov/pubmed/35449559
http://dx.doi.org/10.3389/fnbeh.2022.873466
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