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在精神分裂症中改变了Rbfox1-Vamp1通路和前额叶皮层功能障碍
Youjin Chung1, Samuel Dienel1, Matthew Belch1
1University of Pittsburgh.
Research square
|July 3, 2023
概括
精神分裂症与帕瓦胺表达内部神经元 (PVI) 中的Rbfox1和Vamp1蛋白水平降低有关,损害GABA释放并减少前额叶皮层的马振荡.
科学领域:
- 神经科学是一个神经科学.
- 分子精神病学分子精神病学
- 计算神经科学是一种神经科学.
背景情况:
- 精神分裂症与前额叶皮质 (PFC) 缺陷的马振荡有关,可能是由于帕瓦胺表达性内部神经元 (PVIs) 的抑制驱动力受损.
- 结合RNA的fox-1同源1 (Rbfox1) 调节PVI抑制功能,部分是通过其细胞质异型对囊泡相关膜蛋白1 (Vamp1) 水平的控制以及随后的GABA释放概率.
研究的目的:
- 研究精神分裂症患者的PFC中PVI内的Rbfox1-Vamp1通路的变化.
- 探索这些分子变化对PFC网络活动和马振荡的功能后果.
主要方法:
- 在20对匹配的精神分裂症对和对照对象的PFC组织上利用多标签的现场杂交和免疫组织化学.
- 在PVI中量化了细胞质Rbfox1蛋白和Vamp1mRNA水平.
- 采用计算网络模型来模拟改变GABA释放概率对马功率的影响.
主要成果:
- 与对照人群相比,从精神分裂症患者的PVI中观察到显著较低的细胞质Rbfox1蛋白水平.
- 在PVI中的Vamp1mRNA水平在精神分裂症中也显著降低,与较低的细胞质Rbfox1蛋白相关.
- 计算建模表明,从PVI中减少GABA释放概率,通过破坏网络同步来降低马功率.
结论:
- 在精神分裂症的PFC PVI中,Rbfox1-Vamp1通路受损.
- 这种损伤可能导致前额叶皮层在精神分裂症中的马振荡观察到的缺陷.
- 这些发现突出了在精神分裂症中PVI功能障碍背后的新型分子机制.
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