Selenium mediates exercise-induced adult neurogenesis and reverses learning deficits induced by hippocampal injury and aging
Selenium mediates exercise-induced adult neurogenesis and reverses learning deficits induced by hippocampal injury and aging
复制标题
硒介导运动引起的成人神经发生并逆转海马损伤和衰老引起的学习缺陷
DOI：
10.1016/j.cmet.2022.01.005
复制
发表时间：
2022-03-01
期刊：
影响因子：
29
通讯作者：
Walker, Tara L.
中科院分区：
文献类型：
--
作者：
Leiter, Odette;Zhuo, Zhan;Walker, Tara L.
尽管运动促进神经发生的作用已经被广泛研究，但这种反应背后的分子机制仍然不清楚。在这里，我们认为这是由运动诱导的抗氧化性硒转运蛋白--硒蛋白P(SEPP1)的系统性释放所介导的。利用基因敲除的小鼠模型，我们证实了SEPP1及其受体低密度脂蛋白受体相关蛋白8(LRP8)是运动诱导的成年海马神经发生增加所必需的。体内补硒可促进海马神经前体细胞(NPC)的增殖和成体神经发生。通过饮食补硒来模拟运动的效果，恢复了神经发生，并扭转了与衰老和海马区损伤相关的认知能力下降，这表明潜在的治疗意义。这些结果提供了一种分子机制，将运动诱导的系统环境变化与静止的海马神经前体细胞的激活以及随后它们重新聚集到神经源性轨迹中联系起来。
Although the neurogenesis-enhancing effects of exercise have been extensively studied, the molecular mechanisms underlying this response remain unclear. Here, we propose that this is mediated by the exercise-induced systemic release of the antioxidant selenium transport protein, selenoprotein P (SEPP1). Using knockout mouse models, we confirmed that SEPP1 and its receptor low-density lipoprotein receptor-related protein 8 (LRP8) are required for the exercise-induced increase in adult hippocampal neurogenesis. In vivo selenium infusion increased hippocampal neural precursor cell (NPC) proliferation and adult neurogenesis. Mimicking the effect of exercise through dietary selenium supplementation restored neurogenesis and reversed the cognitive decline associated with aging and hippocampal injury, suggesting potential therapeutic relevance. These results provide a molecular mechanism linking exercise-induced changes in the systemic environment to the activation of quiescent hippocampal NPCs and their subsequent recruitment into the neurogenic trajectory.