CRH-R2信号调节了海马体mHypoA-2/30神经元中的食和昼夜基因表达
Viridiana Alcántara-Alonso1,2, Robert Dallmann1, Hendrik Lehnert3
1Translational Medicine, Warwick Medical School, University of Warwick, Coventry, United Kingdom.
Frontiers in endocrinology
|October 30, 2023
概括
这项研究揭示了下丘脑CRH-R2信号如何影响食欲和昼夜节律,特别是在压力下. 乌洛科丁2增强了Bmal1的表达,可能有助于在活跃的昼夜阶段对厌食反应.
科学领域:
- 神经内分泌学神经内分泌学
- 代谢调节 代谢调节 代谢调节 代谢调节
- 时间生物学 时间生物学
背景情况:
- 脑下垂体皮质激素释放激素受体2 (CRH-R2) 对于压力恢复和食欲控制至关重要.
- 慢性压力可能导致CRH-R2抵抗,改变养行为和信号通路,如CREB酸化.
- 这些压力诱导的CRH-R2信号传递变化背后的分子机制仍然不清楚.
研究的目的:
- 在小鼠下丘脑衍生细胞系 (mHypoA-2/30) 中研究CRH-R2信号传递.
- 检查CRH-R2对养和昼夜调节基因表达的影响.
- 阐明乌罗皮素2 (Ucn2) 对时钟基因和CRH-R2信号传递的影响.
主要方法:
- 利用mHypoA-2/30细胞系研究CRH-R2信号传递.
- 评估了CREB和AMPK的酸化.
- 分析了食欲调节基因 (Pomc,Npy) 和时钟基因 (Bmal1) 的表达.
- 雇佣昼夜生物发光记者来监测时钟基因节律.
主要成果:
- 在mHypoA-2/30细胞中确定了功能性的CRH-R2受体.
- CRH-R2激活不同调节的CREB和AMPK酸化.
- CRH-R2信号调节了Pomc和Npy的表达,与厌氧效应一致.
- 在原生细胞和记者细胞中,ucn2增强了bmal1mRNA水平和节律幅度.
结论:
- 下丘脑中的CRH-R2信号通过Pomc和Npy影响食欲调节.
- Ucn2对Bmal1的影响表明它在压力期间的昼夜食调节中发挥了作用.
- 这些发现为下丘脑CRH-R2信号传递在昼夜养和应激反应的背景下提供了新的见解.
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