与代谢功能障碍相关的脂肪性肝病改变了大脑功能和行为:针对肝脏的siRNA治疗的见解
Teresa Cardoso Delgado1,2,3,4, Celia Martín-Cuevas5,6, Ana C Sánchez Hidalgo5,6
1Liver Disease Lab, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), 48160 Derio, Bizkaia, Spain.
Science advances
|October 22, 2025
概括
与代谢功能障碍相关的脂肪性肝病 (MASLD) 会导致大脑缺陷. 用siRNA-Cnnm4疗法准肝脏代谢恢复了认知和感觉运动功能,揭示了可治疗的肝脑轴.
科学领域:
- 神经科学是一个神经科学.
- 肝病学 肝病学是一种肝病学.
- 代谢障碍 代谢障碍 代谢障碍
背景情况:
- 与代谢功能障碍相关的脂肪性肝病 (MASLD) 与认知和感觉运动问题有关.
- 目前尚不清楚MASLD是否足以引起中枢神经系统的缺陷.
研究的目的:
- 调查MASLD是否足以引起神经行为和海马体功能障碍.
- 探索针对MASLD中的肝脏新陈代谢的治疗潜力.
主要方法:
- 我们使用了饮食诱导的MASLD小鼠模型.
- 神经行为测试评估了社会记忆和感官运动处理.
- 分析了海马的功能,包括神经发生和突触可塑性.
- 使用siRNA治疗对CNNM4.4进行肝脏代谢调节.
主要成果:
- 马斯尔德小鼠表现出社会记忆,感觉运动处理和海马功能受损 (神经元内部神经元,树突脊柱和神经发生减少).
- 针对肝脏新陈代谢的siRNA-Cnnm4疗法逆转了这些缺陷.
- 治疗恢复了海马突触生成,线粒体功能和神经发生相关的基因表达.
结论:
- 在MASLD中的肝病理足以驱动神经行为和海马体功能障碍.
- 针对肝脏代谢的肝脏特异性干预可以恢复大脑功能.
- 对于与MASLD相关的神经并发症,存在一种因果和治疗上可向的肝脑轴.
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