强化性内分泌激素信号的干扰会触发与应激反应一致的细胞,行为和神经内分泌反应
Gavin N Petrie1,2,3, Georgia Balsevich2,3, Tamás Füzesi2
1Neuroscience Program, University of Calgary, Calgary, Alberta, Canada.
British journal of pharmacology
|July 24, 2023
概括
构成性内分泌大麻素 (eCB) 信号通过调节副腹腔核 (PVN) 中的皮质otropin释放激素 (CRH) 神经元来抑制压力反应. 扰乱eCB信号激活了下丘脑-垂体-上腺 (HPA) 轴.
科学领域:
- 神经科学是一个神经科学.
- 内分泌学 在内分泌学.
- 压力生理学 压力生理学
背景情况:
- 内分泌大麻素 (eCB) 信号传递在调节身体应激反应,特别是下丘脑-垂体-上腺 (HPA) 轴中起着至关重要的作用.
- 通过eCB信号影响HPA轴的精确机制,特别是对腹腔内核 (PVN) 中的皮质otropin释放激素 (CRH) 神经元,仍然不完全理解.
研究的目的:
- 调查eCB增强信号在PVN中调节CRH神经元活动中的作用.
- 确定eCB信号中断如何影响HPA轴,并对应激反应产生影响.
主要方法:
- 利用细胞,内分泌和行为评估的组合来评估CRH神经元的激活.
- 使用CB1受体对抗剂 (AM251,NESS243) 和NAPE PLD抑制剂 (LEI401) 来破坏eCB信号传输.
- 将AM251直接注入PVN,并使用光遗传抑制PVN CRH神经元.
主要成果:
- 药物抑制eCB信号传递 (AM251,NESS243,LEI401) 增加了PVN中的Fos表达,诱导了类似压力的行为 (例如理),以及循环皮质 (CORT) 的升高.
- 直接PVN给药AM251模仿了这些效应.
- 对PVN CRH神经元的光遗传抑制减弱了由eCB信号干扰引起的与压力相关的行为变化.
结论:
- 在静止条件下,构成性eCB信号作为PVN中CRH神经元的局部制动作用.
- 这种 tonic eCB 调节对于防止 HPA 轴不适当激活和维持平衡至关重要.
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