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ASD 相关基因 CHD8 的缺失会破坏小鼠的行为模式并抑制海马神经发生。

The Deficiency of the ASD-Related Gene CHD8 Disrupts Behavioral Patterns and Inhibits Hippocampal Neurogenesis in Mice.

机构信息

Medical College, Shanxi Datong University, Datong, 037009, China.

Institute of Respiratory Disease and Occupational Disease, Medical College, Shanxi Datong University, Datong, 037009, China.

出版信息

J Mol Neurosci. 2024 Oct 31;74(4):103. doi: 10.1007/s12031-024-02283-7.

Abstract

Chromodomain helicase DNA-binding 8 (CHD8) is a gene that poses a high risk for autism spectrum disorder (ASD) and neurological development delay. Nevertheless, the impact of CHD8 haploinsufficiency on both hippocampus neurogenesis and behavior remains uncertain. Here, we performed behavioral assessments on male and female CHD8 heterozygous mice. The study discovered that both male and female CHD8 heterozygous mice displayed an impairment in preference for social novelty. Concurrently, CHD8 heterozygous mice exhibited anxiety-like behavior. However, its cognitive capacity for learning and memory is within the expected range. Furthermore, we discovered a reduction in the number of both immature and mature new neurons in mice with CHD8 heterozygous, resulting in an impeded neurogenesis process in the hippocampus. Taken together, our findings indicate that CHD8 plays a crucial role in the regulation of hippocampal neurogenesis, and further suggest that ASD-like behaviors observed in CHD8 heterozygous mice may be associated with disruptions in hippocampal neurogenesis.

摘要

染色质解旋酶 DNA 结合蛋白 8(CHD8)是一种与自闭症谱系障碍(ASD)和神经发育迟缓高度相关的基因。然而,CHD8 杂合不足对海马神经发生和行为的影响仍不确定。在这里,我们对雄性和雌性 CHD8 杂合子小鼠进行了行为评估。研究发现,雄性和雌性 CHD8 杂合子小鼠均表现出对社交新颖性的偏好受损。同时,CHD8 杂合子小鼠表现出焦虑样行为。然而,其学习和记忆的认知能力仍在预期范围内。此外,我们发现 CHD8 杂合子小鼠的不成熟和成熟新神经元数量减少,导致海马神经发生过程受阻。综上所述,我们的研究结果表明 CHD8 在调节海马神经发生中起着至关重要的作用,并进一步表明 CHD8 杂合子小鼠中观察到的 ASD 样行为可能与海马神经发生的破坏有关。

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