Exercise hormone irisin is a critical regulator of cognitive function.
Exercise hormone irisin is a critical regulator of cognitive function.
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DOI：
10.1038/s42255-021-00438-z
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发表时间：
2021-08
影响因子：
20.8
通讯作者：
Wrann, Christiane D.
中科院分区：
文献类型：
--
作者：
Islam, Mohammad R.;Valaris, Sophia;Young, Michael F.;Haley, Erin B.;Luo, Renhao;Bond, Sabrina F.;Mazuera, Sofia;Kitchen, Robert R.;Caldarone, Barbara J.;Bettio, Luis E. B.;Christie, Brian R.;Schmider, Angela B.;Soberman, Roy J.;Besnard, Antoine;Jedrychowski, Mark P.;Kim, Hyeonwoo;Tu, Hua;Kim, Eunhee;Choi, Se Hoon;Tanzi, Rudolph E.;Spiegelman, Bruce M.;Wrann, Christiane D.
识别驱动运动认知益处的分泌介质对于治疗衰老或阿尔茨海默病（AD）中的认知下降具有很大的希望。在这里，我们表明，鸢尾素，运动诱导的膜蛋白FNDC5的切割和循环形式，足以赋予运动对认知功能的益处。FNDC5/irisin的遗传缺失（全局F5KO小鼠）损害运动、衰老和AD中的认知功能。F5KO中减少的模式分离可以通过将鸢尾素直接递送到齿状回中来挽救，这表明鸢尾素是活性部分。在F5KO小鼠中，成年出生的齿状回神经元在形态、转录和功能上都异常。重要的是，通过腺相关病毒在肝脏中过表达通过外周递送鸢尾素来提高循环鸢尾素水平，导致中枢鸢尾素富集，并且足以改善AD小鼠模型中的认知缺陷和神经病理学。Irisin是运动的认知益处的重要调节剂，并且是治疗包括AD在内的认知障碍的潜在治疗剂。
Identifying secreted mediators driving the cognitive benefits of exercise holds great promise for the treatment of cognitive decline in aging or Alzheimer’s disease (AD). Here, we show that irisin, the cleaved and circulating form of the exercise-induced membrane protein FNDC5, is sufficient to confer the exercise benefits on cognitive function. Genetic deletion of FNDC5/irisin (global F5KO mice) impairs cognitive function in exercise, aging, and AD. Diminished pattern separation in F5KOs can be rescued by delivering irisin directly into the dentate gyrus, suggesting that irisin is the active moiety. In F5KO mice, adult-born neurons in the dentate gyrus are morphologically, transcriptionally, and functionally abnormal. Importantly, elevation of circulating irisin levels by peripheral delivery of irisin via adeno-associated viral overexpression in the liver, results in enrichment of central irisin and is sufficient to improve both the cognitive deficit and neuropathology in AD mouse models. Irisin is a crucial regulator of cognitive benefits of exercise and potential therapeutic for treating cognitive disorders including AD.
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