与自闭症相关的ASPM变异在小鼠中引起大脑症和社会认知缺陷
bioRxiv : the preprint server for biology
|March 3, 2025
概括
自闭症谱系障碍 (ASD) 中的大脑与不平衡的刺激-抑制比率有关,而不仅仅是大脑的大小. 这种不平衡会导致类似自闭症的症状,即使没有比例的神经元扩张.
科学领域:
- 神经科学是一个神经科学.
- 遗传学 是一个遗传学.
- 发展生物学 发展生物学
背景情况:
- 自闭症谱系障碍 (ASD) 是一种神经发育障碍,其特点是社会认知缺陷.
- 大脑 (头部周长扩大) 观察到大约20%的严重自闭症患者.
- 大头症在自闭症病原体中的确切作用尚不清楚.
研究的目的:
- 调查宏头症和ASD之间的机械联系.
- 为了检查与ASD相关的 *ASPM* 基因 (与异常状小头症相关的) 新型功能增益突变的影响.
主要方法:
- 使用了*Aspm*功能增益的敲进鼠标模型.
- 分析了神经发生,放射性质扩张和刺激-抑制 (E-I) 神经元比率.
- 评估大脑超连接性和社会认知行为,并注意到男性特异性.
主要成果:
- 具有 *Aspm* 功能增益突变的小鼠表现出大脑症和过度胚胎神经发生.
- 观察到增加了E-I比率和大脑超连接性.
- 雄性小鼠表现出社会认知缺陷.
结论:
- 在ASD中的大脑症与改变的E-I神经元比率有关,而不是所有神经元类型的比例增加.
- *ASPM*基因突变影响皮质发育,导致大脑和类似ASD的表型.
- 巨头症本身可能会导致ASD类症状的一个子集,独立于特定的基因表达模式.
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