在压力诱导的认知功能障碍中,泄漏的神经氨酸受体的作用
Xiaoping Liu1, Matthew J Betzenhauser, Steve Reiken
1Department of Physiology and Cellular Biophysics, Clyde and Helen Wu Center for Molecular Cardiology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
Cell
|September 4, 2012
概括
慢性压力导致大脑的RyR2通道发生故障,损害记忆和学习. 用S107或基因改造稳定这些通道可以挽救认知功能,这表明RyR2是治疗目标.
科学领域:
- 神经科学是一个神经科学.
- 分子生物学分子生物学
- 药理学 药理学是指药理学的学科.
背景情况:
- 2型氨酸受体/释放通道 (RyR2) 在大脑中大量存在.
- 慢性压力会激活神经元中的cAMP信号通路.
- 神经RyR2与压力诱导的认知功能障碍有关.
研究的目的:
- 研究神经元RyR2在慢性压力诱导的认知功能障碍中的作用.
- 确定与压力相关的认知障碍的治疗点.
主要方法:
- 鼠类慢性克制压力模型.
- 对RyR2酸化,氧化和calstabin2相互作用的评估.
- 认知功能的评估,包括学习,记忆和长期增强 (LTP).
- 使用RyR2稳定化合物S107和对RyR2进行基因操纵.
主要成果:
- 慢性压力诱导神经元RyR2重塑,包括PKA酸化,氧化和calstabin2耗尽,导致细胞内泄漏.
- 观察到压力诱导的认知缺陷和海马体LTP降低.
- 口服S107或对RyR2 PKA酸化部位的基因切除挽救了认知功能和LTP.
结论:
- 神经元RyR2重塑显著促进压力诱导的认知功能障碍.
- 泄漏的RyR2通道代表了治疗慢性压力相关的认知障碍的潜在治疗目标.
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