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缺少GPER1导致海马体可塑性和认知功能的性别特异性失调

Aune Koitmäe¹, Yannik Karsten^1,2, Xiaoyu Li^1,3

¹Institute of Neuroanatomy, University Medical Center Hamburg, Hamburg, Germany.

The Journal of endocrinology

|July 3, 2023

概括

与G蛋白结合的雌激素受体1 (GPER1) 在小鼠大脑功能中起着性别特异性的作用. 缺少GPER1会影响焦虑,恐惧反应和空间学习,这表明它与认知和情绪障碍有关.

科学领域:

神经科学是一个神经科学.
内分泌学在内分泌学.
行为遗传学行为遗传学

背景情况:

雌激素通过雌激素受体调节突触可塑性和海马体依赖的认知.
G蛋白结合雌激素受体1 (GPER1) 参与了这些雌激素效应.
了解GPER1的确切作用,特别是性别特异性功能,对于阐明认知和情绪障碍机制至关重要.

研究的目的:

调查GPER1在焦虑,恐惧条件,空间学习和记忆中的性别特异性作用.
检查GPER1对海马突触功能影响的生理基础.
为了将GPER1的影响与女性雌性周期的不同阶段相关联.

主要方法:

使用了GPER1-Knockout (GPER1-KO) 的小鼠和野生类型的 littermates.
使用升高的加迷宫评估类似焦虑的行为.
通过情境恐惧调节和空间学习/记忆与莫里斯水迷宫评估恐惧反应.
在海马的CA1区域测量了突触刺激能力.
关键突触蛋白质的海马表达量化,包括GluA1和spinophilin.

主要成果:

GPER1-KO男性表现出减少的焦虑,而GPER1-KO女性表现出增加的恐惧反应.
在GPER1-KO小鼠的两性中,空间学习和记忆巩固受损.
在女性中,缺陷在高雌激素阶段 (孕期/孕期) 中加剧.
在GPER1-KO雄性和高雌激素雌性中,海马CA1突触刺激性增加.
在GPER1-KO小鼠中观察到GluA1和斯皮诺菲林的改变表达,其模式取决于性别和周期.

结论:

GPER1对海马网络功能产生调节性和性别特异性影响,一般降低神经元刺激性.
对GPER1的功能失调可能会导致特定于性别的认知障碍和情绪障碍.
这些发现突出了GPER1作为神经和精神疾病的潜在治疗点.

关键词:

在AMPA受体上,AMPA受体是在 LTP LTP 中.恐惧的条件化是恐惧的条件化.在海马体内,海马体空间学习空间学习类固醇激素是类固醇激素激素的类固醇激素.

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