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

IF 2.8 4区 医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Xiaojie Niu, Feifei Huang, Haizhen Lyu, Jiao Liu, Xinwei Zhang, Jiang Bian, Zhijie Gao, Binyu Liu
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引用次数: 0

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.

ASD 相关基因 CHD8 的缺失会扰乱小鼠的行为模式并抑制海马神经元的形成。
染色体域螺旋酶 DNA 结合 8(CHD8)是一种导致自闭症谱系障碍(ASD)和神经系统发育迟缓的高风险基因。然而,CHD8单倍体缺陷对海马神经发生和行为的影响仍不确定。在这里,我们对雌雄CHD8杂合子小鼠进行了行为评估。研究发现,雌雄CHD8杂合子小鼠均表现出对社会新事物的偏好障碍。同时,CHD8杂合子小鼠表现出类似焦虑的行为。然而,其学习和记忆认知能力却在预期范围内。此外,我们还发现,CHD8 杂合子小鼠体内未成熟和成熟的新神经元数量都有所减少,导致海马的神经发生过程受阻。综上所述,我们的研究结果表明,CHD8 在海马神经发生的调控过程中起着至关重要的作用,并进一步表明,在 CHD8 杂合子小鼠中观察到的 ASD 类行为可能与海马神经发生的破坏有关。
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来源期刊
Journal of Molecular Neuroscience
Journal of Molecular Neuroscience 医学-神经科学
CiteScore
6.60
自引率
3.20%
发文量
142
审稿时长
1 months
期刊介绍: The Journal of Molecular Neuroscience is committed to the rapid publication of original findings that increase our understanding of the molecular structure, function, and development of the nervous system. The criteria for acceptance of manuscripts will be scientific excellence, originality, and relevance to the field of molecular neuroscience. Manuscripts with clinical relevance are especially encouraged since the journal seeks to provide a means for accelerating the progression of basic research findings toward clinical utilization. All experiments described in the Journal of Molecular Neuroscience that involve the use of animal or human subjects must have been approved by the appropriate institutional review committee and conform to accepted ethical standards.
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