这种LH受体调节海马体空间记忆,并恢复了卵巢切除的APP/PS1AD小鼠的树突脊柱密度
bioRxiv : the preprint server for biology
|January 8, 2024
概括
用人类胆性淋巴激素 (hCG) 激活黄素激素受体 (LHCGR) 改善了阿尔茨海默氏病病理学的雌性小鼠的空间记忆和大脑细胞连接,无论其更年期状态如何.
科学领域:
- 神经科学是一个神经科学.
- 内分泌学 在内分泌学.
- 阿尔茨海默氏症疾病研究研究
背景情况:
- 化激素受体 (LHCGR) 的激活可以改善记忆和神经元连接.
- 它对阿尔茨海默病 (AD) 大脑和潜在机制的影响尚不清楚.
研究的目的:
- 研究APP/PS1AD小鼠模型中中央LHCGR激活的治疗潜力,特别是在绝经后的状态.
- 阐明LHCGR激活影响认知功能,Aβ病理和海马体结构的机制.
主要方法:
- 人类胆性淋巴激素 (hCG),一个LHCGR激动剂,被用脑内静脉注射 (ICV) 给生殖性完整和卵巢切除的APP/PS1雌性小鼠.
- 用莫里斯水迷宫评估认知功能.
- 分析了海马体树突性脊柱密度,Aβ病理以及相关的信号通路.
主要成果:
- 中央LHCGR激活恢复了被卵巢切除的APP/PS1小鼠的空间记忆,使其恢复到野生类型的水平,而不会影响Aβ病理.
- 激活LHCGR显著增加了海马体树突脊柱密度,无论是生殖完整和卵巢切除的小鼠.
- 卵巢切除术诱导的 APP/PS1 大脑中的炎症性基因增加被LHCGR激活抑制,可能会调解认知和 BDNF 效应.
结论:
- 中央LHCGR激活对更年期阿尔茨海默病大脑认知能力下降具有治疗潜力.
- 通过BDNF依赖和独立的途径,LHCGR激动性增强了认知功能和海马体结构.
- 激活LHCGR可以减轻卵巢切除术引起的炎症,有助于其认知益处.
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