Neural Hyperactivity Is a Core Pathophysiological Change Induced by Deletion of a High Autism Risk Gene Ash1L in the Mouse Brain.
Neural Hyperactivity Is a Core Pathophysiological Change Induced by Deletion of a High Autism Risk Gene Ash1L in the Mouse Brain.
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DOI：
10.3389/fnbeh.2022.873466
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发表时间：
2022
影响因子：
3
通讯作者：
He J
中科院分区：
文献类型：
--
作者：
Gao Y;Aljazi MB;He J
ASH 1 L是与自闭症谱系障碍（ASD）和智力残疾（ID）相关的最高风险基因之一。我们最近的研究表明，小鼠大脑中Ash 1 l的缺失足以诱导ASD/ID样行为和认知缺陷，这表明破坏性ASH 1 L突变可能与ASD/ID的发生呈正相关。然而，核心的病理生理变化在阿什11缺乏的大脑仍然在很大程度上未知。在这里，我们表明，在小鼠大脑中的Ash 1 l的损失导致运动过度活跃，高代谢活动，和多动相关的睡眠和脂质代谢的变化。此外，突变小鼠对惊厥剂诱导的癫痫表现出较低的阈值，并且多个大脑区域的神经元活动增加。因此，我们目前的研究表明，神经功能亢进是一个核心的病理生理变化，在阿什11缺陷小鼠的大脑，这可能是一个大脑水平的机制，导致阿什11缺失诱导的脑功能异常和自闭症样行为缺陷。
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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影响因子：
2.5
作者：
BULLITT, E
通讯作者：
BULLITT, E
影响因子：
2.6
作者：
Van Erum, Jan;Van Dam, Debby;De Deyn, Peter Paul
通讯作者：
De Deyn, Peter Paul
影响因子：
3.3
作者：
Tagaito, Y;Polotsky, VY;O'Donnell, CP
通讯作者：
O'Donnell, CP
自闭症谱系障碍。
DOI：
10.1038/s41572-019-0138-4
发表时间：
2020-01-16
期刊：
Nature reviews. Disease primers
影响因子：
--
作者：
Lord C;Brugha TS;Charman T;Cusack J;Dumas G;Frazier T;Jones EJH;Jones RM;Pickles A;State MW;Taylor JL;Veenstra-VanderWeele J
通讯作者：
Veenstra-VanderWeele J
影响因子：
5.9
作者：
Gao Y;Duque-Wilckens N;Aljazi MB;Wu Y;Moeser AJ;Mias GI;Robison AJ;He J
通讯作者：
He J