线粒体功能障碍揭示了H2S介导的突触硫化作为自闭症相关社会缺陷的潜在机制
Panpan Xian1, Mengmeng Wang2, Rougang Xie2
1Department of Neurobiology, Institute of Neurosciences, School of Basic Medicine, Fourth Military Medical University, Xi'an, Shaanxi 710032, China; Department of Neurology, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710038, China.
Cell metabolism
|September 4, 2025
概括
大脑中硫化 (H2S) 和蛋白质硫化的增加
科学领域:
- 神经科学
- 生物化学
- 遗传学
背景情况:
- 在自闭症患者的外周组织中观察到线粒体功能障碍.
- 神经元代谢在自闭症中的作用尚不清楚.
研究的目的:
- 在自闭症模型中研究神经元代谢和硫化 (H2S).
- 探索H2S对突触功能和社会行为的影响.
主要方法:
- 在Shank3b-/和Fmr1-/y小鼠模型中专注于前带皮层 (ACC).
- 评估了突触传播,社会功能和蛋白质硫化.
- 使用囊胺β合成酶 (CBS) 操纵和硫氨基酸限制.
主要成果:
- 在这两种自闭症模型中的ACC神经元中,H2S水平升高.
- 中枢神经系统过度表达损害了突触功能和社会行为;
- 包括mGluR5在内的突触蛋白的硫化被改变;mGluR5的硫化消去部分挽救了社会缺陷.
- 在小鼠模型和人类神经元中,硫氨基酸限制改善了社会和突触缺陷.
结论:
- 过度的H2S和突触蛋白硫化是自闭症相关的社会功能障碍的潜在机制.
- 针对H2S代谢和蛋白质硫化可能为自闭症提供治疗策略.
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