更年期女性认知功能减退严重影响她们的生活质量，雌激素替代治疗能够有效改善认知功能，但副作用限制其临床应用，亟待发掘疗效好且安全的药物和干预策略。运动能够有效改善更年期综合征包括认知功能减退，鸢尾素（Irisin）作为运动时肌肉产生的新激素，在神经元分化、发育和成熟过程中发挥重要作用，并具有神经保护和抗抑郁作用。我们前期预实验发现，去势小鼠学习记忆减退并伴随血清中雌激素和鸢尾素水平的降低，外源性补充鸢尾素能够改善去势小鼠学习记忆，同时增加血清中雌激素水平。据此，本项目提出假说：鸢尾素通过调控雌激素水平改善去势小鼠认知障碍。本课题拟采用行为学、电生理学、分子生物学、药理学以及病毒敲除等技术，深入探究鸢尾素是运动改善去势小鼠认知障碍作用的重要分子，阐明雌激素介导鸢尾素作用的潜在分子机制。本课题为运动改善认知功能完善理论基础，同时为治疗女性更年期认知障碍提供新策略和潜在药物靶点。

Cognitive impairment of menopausal women seriously affects their quality of life. Estrogen replacement therapy can effectively improve cognitive function, but the side effects limit its clinical application. So it is urgent to explore effective and safe drugs and intervention strategies. Irisin, a new hormone produced by muscles during exercise, plays an important role in neuron differentiation, development and maturation, and it has neuroprotective and antidepressant effects. In our preliminary experiment, we found that the learning and memory was declined in ovariectomized mice, along with the decreased levels of estrogen and irisin in serum. The exogenous supplement of irisin can improve the learning and memory of ovariectomized mice and increase the estrogen level in serum. Accordingly, we hypothesize that irisin can improve the cognitive impairment of ovariectomized mice by regulating estrogen level. In present study, behavioral, electrophysiological, molecular biological, pharmacological and gene knockdown technologies will be used to explore the role of irisin in exercise induced cognition improvement in ovariectomized mice, and to elucidate the potential molecular mechanism of irisin mediated by estrogen. This project will provide the theoretical basis for exercise-induced cognitive improvement, as well as new therapeutic strategies and potential drug targets for the treatment of female cognitive impairment in menopause.