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线粒体介导的新陈代谢和微生物群的生物多样性影响自闭症类行为
Yunyi Yao1, Brandon O'Sullivan2, Tapan K Mondal1
1Wadsworth Center, New York State Department of Health, Albany, USA.
概括
线粒体DNA转移通过改变肠道微生物群和大脑胆固醇,改善了BTBR小鼠的自闭症谱系障碍 (ASD) 行为. 这突显了线粒体在神经发育和免疫力中的作用.
科学领域:
- 神经科学是一个神经科学.
- 遗传学 是一个遗传学.
- 免疫学 免疫学 免疫学
背景情况:
- BTBR小鼠表现出与线粒体功能障碍相关的自闭症谱系障碍 (ASD) 类行为.
- 使用BTBR核DNA和C57BL/6J (B6) 线粒体创建了一个新的小鼠模型,BTBR-mtB6,它具有正常的行为和免疫力.
- 与BTBR小鼠相比,BTBR-mtB6菌株表现出正常化的行为和免疫特征.
研究的目的:
- 研究BTBR-mtB6小鼠的行为和免疫学改善背后的机制.
- 探索线粒体置换对肠道微生物群,代谢和相关生理变化的影响.
主要方法:
- 使用测序分析便微生物组合的分析.
- 对遗传和分子变化的检测,包括血液和器官 (大脑,肝脏) 的代谢学.
- 免疫细胞群 (T细胞) 和蛋白质水平 (PPARγ,复合IV,IgG) 的评估.
主要成果:
- 在BTBR,B6和BTBR-mtB6菌株中观察到明显的便微生物组概况.
- 在BTBR-mtB6小鼠中的血清和脑胆固醇水平在BTBR和B6小鼠之间是中间的.
- 肝脏PPARγ水平和白色脂肪组织T细胞数量是中间的,这表明脂质代谢和免疫反应发生了变化.
结论:
- 线粒体DNA的替代影响便微生物群,新陈代谢和大脑髓化 (MBP,CNPase表达).
- 在BTBR-mtB6小鼠中的代谢物和微生物组变化与影响代谢,免疫力和行为的线粒体核相互作用有关.
- 这些发现强调了线粒体在调节与ASD相关的复杂表型方面的关键作用.
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