卵巢功能丧失和雌激素治疗重塑大脑的突触和代谢蛋白质组
Sebastian F Salathe1, Edziu Franczak1, Zane Busick1
1Department of Cell Biology and Physiology, University of Kansas Medical Center, Kansas City KS, USA.
bioRxiv : the preprint server for biology
|November 24, 2025
概括
雌激素疗法 (E2) 通过保存对突触功能和新陈代谢至关重要的蛋白质,有助于在更年期期间保持大脑健康. E2治疗还可以防止与卵巢激素损失相关的线粒体能量生产下降.
科学领域:
- 神经科学是一个神经科学.
- 内分泌学 在内分泌学.
- 代谢学 代谢学 代谢学
背景情况:
- 更年期与认知能力下降和大脑新陈代谢减少有关.
- 雌激素 (E2) 治疗可以减轻这些更年期影响.
- 了解雌激素神经保护的分子机制对于女性的大脑健康至关重要.
研究的目的:
- 研究卵巢激素损失和E2治疗对老年雌性小鼠大脑蛋白质组和线粒体功能的影响.
- 为了确定受更年期和E2治疗影响的特定蛋白质和代谢途径.
主要方法:
- 年龄较大的雌性C57BL/6J小鼠接受了假或卵巢切除 (OVX) 手术.
- 在OVX小鼠中,小鼠被食高脂肪饮食,然后接受E2或载体治疗.
- 进行了大脑同质体的蛋白质组分析和线粒体呼吸和酶活性的评估.
主要成果:
- E2 调节了 4,992 种蛋白质,增强了突触生成信号.
- OVX减少了参与突触功能,新陈代谢 (氨基酸,,TCA循环) 和氧化酸化 (OxPhos) 的蛋白质.
- 取代E2恢复了这些通路中的蛋白质表达,改善了复杂IV活性,但没有改变基底/状态3呼吸.
结论:
- 雌激素 (E2) 通过维护突触完整性和代谢蛋白质,对维持大脑健康至关重要.
- E2减轻了与更年期相关的线粒体生物能量的下降.
- 这些发现支持E2疗法作为一种策略,以维持经更年期妇女的认知功能和大脑代谢.
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