对于典型的青春期和雌性小鼠的生殖功能来说,需要从瘦素受体细胞中进行谷氨酸神经传递
Cristina Sáenz de Miera1, Nicole Bellefontaine1, Susan J Allen1
1Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, 48109-5622, USA.
bioRxiv : the preprint server for biology
|October 4, 2023
概括
从下丘脑中瘦素敏感神经元传递的谷氨酸信号对于生殖控制至关重要. 这项研究表明,Vglut2对于瘦素是必需的.
科学领域:
- 神经内分泌学神经内分泌学
- 生殖生物学 生殖生物学
- 代谢调节 代谢调节 代谢调节
背景情况:
- 垂体腹前乳母细胞核 (PMv) 在代谢控制生殖过程中发挥作用.
- 在表达Vglut2的PMv神经元中,瘦素受体 (LepRb) 信号传递的确切作用尚未完全理解.
研究的目的:
- 为了研究从素敏感的PMv神经元中的谷氨酸信号传递在青春期和生育能力中的作用.
- 为了确定白通过PMv神经元对青春期发育的作用是否依赖于Vglut2.2.
主要方法:
- 在LepRb-Cre小鼠中,专门由设计药物 (DREADDs) 激活的利用设计受体刺激PMv神经元并测量素激素 (LH) 释放.
- 产生的LepRb缺乏小鼠与Vglut2删除 (LepR) 和救援实验涉及表达Cre重组酶的腺相关病毒的立体毒性注射,以评估青春期的发展和生育能力.
主要成果:
- 在成年女性中,PMv神经元的刺激诱导LH释放,与c-Fos表达相关.
- LepR小鼠表现出延迟的青春期,破坏的雌性周期,增加的GnRH和LH反应受损,表明GnRH释放受损.
- 在PMv中拯救Lepr和Vglut2删除恢复了对照小鼠的青春期发育和生育能力,而LepR;Vglut2小鼠显示没有青春期发育.
结论:
- 对于调节生殖轴来说,从对叶丁敏感的PMv神经元发出的谷氨酸信号是必不可少的.
- 莱普对由PMv神经元介导的青春期发育的作用需要Vglut2-依赖的谷氨酸信号传递.
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