运动锻炼对雌激素缺乏所致抑郁样行为的影响及其机制研究

Menopausal women have a high incidence of depression, but there is still a lack of safety of the treatment program. In our preliminary study, we found that estrogen deficiency induced depression-like behavior, which might be partly due to the proinflammatory state in the brain. We also found exercise can ameliorate depression-like behavior induced by estrogen deficiency. Based on these results, the objectives of present study are to investigate whether exercise alleviates the depression-like behavior induced by estrogen deficiency by using the ovariectomized rat model, and then to determine the mechanisms involved in depression-like behavior induced by estrogen deficiency through inflammation, further to explore the mechanisms involved in the anti-depression effects of exercise in ovariectomized rats. This study will help further clarify the mechanisms underlying the protective effects of exercise against estrogen deficiency-induced depression, thus provide a theoretical basis for the movement to improve menopausal depression and neuropsychiatric diseases, meanwhile offering alternative non-drug interventions for these disorders.

女性到更年期时，由于雌激素缺乏易患抑郁症，但雌激素缺乏导致抑郁的机制尚未完全阐明，目前对其防治也缺乏更安全有效的方案。我们前期研究发现，雌激素缺乏可能通过促进脑内炎症进而导致抑郁样行为，运动锻炼能缓解雌激素缺乏所致抑郁样行为。本项目将在前期工作基础上，应用去卵巢大鼠模型，系统研究运动锻炼是否可改善雌激素缺乏所致抑郁样行为、雌激素缺乏通过炎症导致抑郁样行为的分子机制、运动锻炼是否通过改善炎症、增加局部雌激素信号而抗抑郁。本项目有助于阐明运动锻炼改善雌激素缺乏所致抑郁样行为的分子机制，并为运动锻炼作为女性更年期抑郁症等神经精神疾病的辅助治疗手段提供理论依据。

女性到更年期时，由于雌激素缺乏易患抑郁症，但雌激素缺乏导致抑郁的机制尚未完全阐明，目前对其防治也缺乏更安全有效的方案。我们的研究发现，雌激素缺乏可能通过促进脑内NLRP3炎性小体激活而促使炎症反应以及抑制脑源性神经生长因子（BDNF）进而导致抑郁样行为，运动锻炼能缓解雌激素缺乏所致抑郁样行为，且还可抑制NLRP3炎性小体激活以及促进了脑内BDNF的生成。此外，运动锻炼也可提高去卵巢动物血中雌激素水平，提示了运动锻炼可促进卵巢外组织产生雌激素。运动锻炼改善抑郁样行为也部分与促使卵巢外组织产生雌激素有关。本研究结果初步阐明了运动锻炼改善雌激素缺乏所致抑郁样行为的分子机制，并为运动锻炼作为女性更年期抑郁症等神经精神疾病的辅助治疗手段提供了理论依据。