下丘脑-垂体-上腺轴的禁食激活的神经基础
Amelia M Douglass1, Jon M Resch1,2, Joseph C Madara1
1Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Nature
|July 26, 2023
概括
禁食会激活下丘脑中的AgRP神经元, 这些神经元对于应激反应至关重要. 这些神经元通过抑制独立于饥饿的GABAergic信号来消毒HPA轴.
科学领域:
- 神经科学
- 内分泌学
- 代谢过程
背景情况:
- 禁食会引发适应性生存,包括下丘脑-垂体-上腺 (HPA) 轴的激活.
- 在禁食期间驱动HPA轴激活的神经机制在很大程度上是未知的.
- 艾古蒂相关 (AgRP) 表达神经元是已知的饥饿调节剂,但它们在应激反应中的作用尚不清楚.
研究的目的:
- 阐明禁食诱导HPA轴激活的神经机制.
- 确定AgRP神经元在HPA轴对禁食反应中的作用.
- 确定AgRP神经元调节神经元活动的新途径.
主要方法:
- 在禁食模型中利用AgRP神经元的基因操纵.
- 研究了从AgRP神经元到副静脉下丘脑 (PVH) 的神经元投射.
- 研究了GABAergic信号和GABA-B受体在AgRP神经元介导的HPA轴激活中的作用.
主要成果:
- 禁食激活的AgRP神经元对于HPA轴的激活至关重要.
- AgRP神经元向PVH投射,并从结核 (BNST) 的床核中预突触抑制GABAergic附属物.
- 在PVH中释放皮质素激素 (CRH) 表达神经元的这种消抑制激活HPA轴,独立于饥饿诱导.
结论:
- 确定AgRP神经元是禁食诱导HPA轴激活的关键驱动因素.
- 通过抑制性附带体的前突触抑制发现了神经元激活的新机制.
- 表明BNST抑制度降低可能是禁食和压力激活HPA轴的常见途径.
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