Institute of Bioscience & Integrative Medicine, Daejeon Korean Hospital of Daejeon University, Daedukdae-ro 176 bun-gil 75, Daejeon, 35235, Republic of Korea.
Department of Korean Rehabilitation Medicine, Daejeon Korean Hospital of Daejeon University, Daedukdae-ro 176 bun-gil 75, Daejeon, 35235, Republic of Korea.
Sci Rep. 2024 Mar 21;14(1):6854. doi: 10.1038/s41598-024-57611-z.
The high risk of neurological disorders in postmenopausal women is an emerging medical issue. Based on the hypothesis of altered estrogen receptors (ERα and β) after the decline of estrogen production, we investigated the changes in ERs expressions across brain regions and depressive/amnesic behaviors. C57BL/6J female mice were ovariectomized (OVX) to establish a menopausal condition. Along with behavior tests (anxiety, depression, and memory), the expression of ERs, microglial activity, and neuronal activity was measured in six brain regions (hippocampus, prefrontal cortex, striatum, raphe nucleus, amygdala, and hypothalamus) from 4 to 12 weeks after OVX. Mice exhibited anxiety- and depressive-like behaviors, as well as memory impairment. These behavioral alterations have been linked to a suppression in the expression of ERβ. The decreased ERβ expression coincided with microglial-derived neuroinflammation, as indicated by notable activations of Ionized calcium-binding adapter molecule 1 and Interleukin-1beta. Additionally, the activity of brain-derived neurotrophic factor (BDNF), particularly in the hippocampus, decreased in a time-dependent manner from 4 to 12 weeks post-OVX. Our study provides evidence shedding light on the susceptibility to memory impairment and depression in women after menopause. This susceptibility is associated with the suppression of ERβ and alteration of ERα in six brain regions.
绝经后女性患神经紊乱疾病的风险很高，这是一个新出现的医学问题。基于雌激素产生下降后雌激素受体（ERα和β）改变的假说，我们研究了 ERs 在大脑各个区域的表达变化以及抑郁/健忘行为。C57BL/6J 雌性小鼠被卵巢切除（OVX）以建立绝经状态。在进行行为测试（焦虑、抑郁和记忆）的同时，我们测量了六个脑区（海马体、前额叶皮层、纹状体、中缝核、杏仁核和下丘脑）中 ERs、小胶质细胞活性和神经元活性在 OVX 后 4 到 12 周的表达情况。小鼠表现出焦虑和抑郁样行为以及记忆障碍。这些行为改变与 ERβ表达抑制有关。ERβ表达的减少与小胶质细胞衍生的神经炎症一致，Ionized calcium-binding adapter molecule 1 和 Interleukin-1beta 的显著激活表明了这一点。此外，脑源性神经营养因子（BDNF）的活性，特别是在海马体中，从 OVX 后 4 周到 12 周呈时间依赖性下降。我们的研究提供了证据，表明绝经后女性易患记忆障碍和抑郁症。这种易感性与 ERβ的抑制和六个脑区中 ERα的改变有关。
