在雌性小鼠中,雌激素激活大脑的MC4R信号来驱动身体活动
William C Krause1, Ruben Rodriguez1, Bruno Gegenhuber2,3
1Department of Cellular and Molecular Pharmacology, School of Medicine, University of California San Francisco, San Francisco, CA, USA.
Nature
|October 14, 2021
概括
雌激素水平下降导致不活动和肥胖. 在VMHvl中,雌激素敏感的神经元通过影响黑色皮质-4受体 (MC4R) 信号来调节能量平衡和身体活动.
科学领域:
- 神经内分泌学
- 代谢调节
- 行为神经科学
背景情况:
- 在动物和人类中,雌激素缺乏与不活动,脂肪积累和糖尿病有关.
- 雌激素的代谢效果,包括能耗调节,随着年龄的增长而下降.
- 排卵前雌激素的激增会暂时增加动物的能量消耗和体力活动.
研究的目的:
- 研究腹侧腹中下丘脑核 (VMHvl) 中对雌激素敏感的神经元在能量分配和体力活动中的作用.
- 阐明雌激素影响能量消耗和行为的机制.
- 探索黑色皮质素-4受体 (MC4R) 信号与雌激素对新陈代谢的影响之间的联系.
主要方法:
- 在雌激素贫乏的小鼠中利用化学遗传来刺激表达MC4R和ERα的VMH1神经元.
- 采用CRISPR介导的激活来研究对身体活动的长期影响.
- 研究了雌激素受体-α (ERα) 对Mc4r基因的直接招募.
主要成果:
- 一组VMH1神经元向兴奋中心发射, 调节雌激素的能量分配.
- 雌激素激增增加了VMH1神经元中的MC4R信号,通过将ERα招募到Mc4r基因.
- 化学遗传刺激逆转了久坐不动的行为和肥胖;CRISPR激活增加了身体活动.
结论:
- 依赖雌激素的VMH1神经元调节能量分配和身体活动.
- MC4R信号传递超出了食物摄入范围,影响行为和新陈代谢.
- 这种荷尔蒙节点突出了雌激素在激发女性行为和维持活动方面的作用.
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