Estrogen receptor beta in astrocytes modulates cognitive function in mid-age female mice.
Estrogen receptor beta in astrocytes modulates cognitive function in mid-age female mice.
复制标题
星形胶质细胞中的雌激素受体β调节中年雌性小鼠的认知功能。
DOI：
10.1038/s41467-023-41723-7
复制
发表时间：
2023-09-28
影响因子：
16.6
通讯作者：
Voskuhl, Rhonda R.
中科院分区：
文献类型：
--
作者：
Itoh, Noriko;Itoh, Yuichiro;Meyer, Cassandra E.;Suen, Timothy Takazo;Cortez-Delgado, Diego;Lomeli, Michelle Rivera;Wendin, Sophia;Somepalli, Sri Sanjana;Golden, Lisa C.;MacKenzie-Graham, Allan;Voskuhl, Rhonda R.
更年期与认知缺陷和脑萎缩有关，但大脑区域和细胞特异性机制尚未完全了解。在这里，我们确定了性激素的年龄相互作用，即在中年，但不是年轻的雌性小鼠卵巢激素的损失，诱导海马依赖性认知功能障碍，背海马萎缩，星形胶质细胞和小胶质细胞激活与突触损失。在性腺完整的雌性小鼠中，选择性删除星形胶质细胞中的雌激素受体β（ERβ），而不是神经元中的雌激素受体β（ERβ），诱导了相同的大脑效应。中年雌性星形胶质细胞-ER β条件性敲除（cKO）小鼠海马星形胶质细胞中基因表达的RNA测序和途径分析显示，葡萄糖异生I和糖酵解I是最差异表达的途径。中年星形胶质细胞-ER β cKO雌性小鼠和绝经后女性的海马中烯醇化酶1基因表达均增加。功能获得研究表明，中年雌性小鼠的ERβ配体治疗逆转了背海马神经病理学。在这里，作者在中年雌性小鼠中显示，星形胶质细胞中雌激素受体β的缺失诱导认知障碍、海马萎缩、神经胶质激活和突触丢失。ERβ配体治疗恢复了这些动物的认知能力并减少了神经病理学。
Menopause is associated with cognitive deficits and brain atrophy, but the brain region and cell-specific mechanisms are not fully understood. Here, we identify a sex hormone by age interaction whereby loss of ovarian hormones in female mice at midlife, but not young age, induced hippocampal-dependent cognitive impairment, dorsal hippocampal atrophy, and astrocyte and microglia activation with synaptic loss. Selective deletion of estrogen receptor beta (ERβ) in astrocytes, but not neurons, in gonadally intact female mice induced the same brain effects. RNA sequencing and pathway analyses of gene expression in hippocampal astrocytes from midlife female astrocyte-ERβ conditional knock out (cKO) mice revealed Gluconeogenesis I and Glycolysis I as the most differentially expressed pathways. Enolase 1 gene expression was increased in hippocampi from both astrocyte-ERβ cKO female mice at midlife and from postmenopausal women. Gain of function studies showed that ERβ ligand treatment of midlife female mice reversed dorsal hippocampal neuropathology. Here the authors show in female mice at mid-life that deletion of estrogen receptor β in astrocytes induced cognitive impairment, hippocampal atrophy, glial activation and synaptic loss. ERβ ligand treatment restored cognition and decreased neuropathology in these animals.
登录
查看更多内容
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
16.2
作者：
Fanselow, Michael S.;Dong, Hong-Wei
通讯作者：
Dong, Hong-Wei
影响因子：
14
作者：
Chang, Rui;Trushina, Eugenia;Zhu, Kuixi;Zaidi, Syed Shujaat Ali;Lau, Branden M.;Kueider-Paisley, Alexandra;Moein, Sara;He, Qianying;Alamprese, Melissa L.;Vagnerova, Barbora;Tang, Andrew;Vijayan, Ramachandran;Liu, Yanyun;Saykin, Andrew J.;Brinton, Roberta D.;Kaddurah-Daouk, Rima
通讯作者：
Kaddurah-Daouk, Rima
DOI：
10.1186/s13195-017-0305-3
发表时间：
2017-09-21
期刊：
Alzheimer's research & therapy
影响因子：
--
作者：
Chhibber A;Zhao L
通讯作者：
Zhao L
DOI：
10.1093/bioinformatics/btu781
发表时间：
2015-04-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Gaidatzis D;Lerch A;Hahne F;Stadler MB
通讯作者：
Stadler MB