Vargas Kris G, Milic Jelena, Zaciragic Asija, Wen Ke-Xin, Jaspers Loes, Nano Jana, Dhana Klodian, Bramer Wichor M, Kraja Bledar, van Beeck Ed, Ikram M Arfan, Muka Taulant, Franco Oscar H
Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands.
Medical Library, Erasmus MC, Rotterdam, The Netherlands.
Maturitas. 2016 Nov;93:41-57. doi: 10.1016/j.maturitas.2016.05.014. Epub 2016 Jun 4.
Females have unique and additional risk factors for neurological disorders. Among classical estrogen receptors, estrogen receptor beta (ERβ) has been suggested as a therapeutic target. However, little is known about the role of ERβ in the female brain. Six electronic databases were searched for articles evaluating the role of ERβ in the female brain and the influence of age and menopause on ERβ function. After screening 3186 titles and abstracts, 49 articles were included in the review, all of which were animal studies. Of these, 19 focused on cellular signaling, 7 on neuroendocrine pathways, 8 on neurological disorders, 4 on neuroprotection and 19 on psychological and psychiatric outcomes (6 studies evaluated two or more outcomes). Our findings showed that ERβ phosphorylated and activated intracellular second messenger proteins and regulated protein expression of genes involved in neurological functions. It also promoted neurogenesis, modulated the neuroendocrine regulation of stress response, conferred neuroprotection against ischemia and inflammation, and reduced anxiety- and depression-like behaviors. Targeting ERβ may constitute a novel treatment for menopausal symptoms, including anxiety, depression, and neurological diseases. However, to establish potential therapeutic and preventive strategies targeting ERβ, future studies should be conducted in humans to further our understanding of the importance of ERβ in women's mental and cognitive health.
女性患有神经疾病有独特且额外的风险因素。在经典雌激素受体中，雌激素受体β（ERβ）已被视为一个治疗靶点。然而，人们对ERβ在女性大脑中的作用知之甚少。检索了六个电子数据库，查找评估ERβ在女性大脑中的作用以及年龄和绝经对ERβ功能影响的文章。在筛选了3186个标题和摘要后，49篇文章被纳入综述，所有这些都是动物研究。其中，19篇关注细胞信号传导，7篇关注神经内分泌途径，8篇关注神经疾病，4篇关注神经保护，19篇关注心理和精神结果（6项研究评估了两种或更多结果）。我们的研究结果表明，ERβ使细胞内第二信使蛋白磷酸化并激活，调节参与神经功能的基因的蛋白表达。它还促进神经发生，调节应激反应的神经内分泌调节，赋予对缺血和炎症的神经保护作用，并减少焦虑样和抑郁样行为。靶向ERβ可能构成一种治疗绝经症状（包括焦虑、抑郁和神经疾病）的新方法。然而，为了制定针对ERβ的潜在治疗和预防策略，未来应在人体中开展研究，以进一步了解ERβ在女性心理和认知健康中的重要性。
