Exercise plasma dampens brain inflammation via clusterin and boosts memory

We discovered “runner” plasma, collected from voluntarily running mice, infused into sedentary mice recapitulates the cellular and functional benefits of exercise on the adult brain. Importantly, runner plasma reduces baseline neuroinflammatory gene expression and experimentally induced brain inflammation. Plasma proteomic analysis revealed a striking increase in complement cascade inhibitors including clusterin (CLU), which is facilitating the anti-inflammatory effects of runner plasma. Intravenously injected CLU strongly binds to brain endothelial cells reducing their inflammatory gene expression in an acute model of brain inflammation and in Alzheimer’s disease model mice. These findings demonstrate the existence of anti-inflammatory “exercise factors” that are transferrable, target the cerebrovasculature and benefit the brain. Identifying transcriptomic changes induced by exogenous clusterin on brain endothelial cells in two mouse models of acute (LPS) or chronic (APP) inflammation

我们发现，将从主动跑步小鼠（voluntarily running mice）中采集的跑步血浆（runner plasma）输注至久坐小鼠体内后，可重现运动对成年大脑的细胞层面与功能层面益处。尤为关键的是，该血浆可降低基线神经炎症基因表达水平，并缓解实验诱导性大脑炎症。血浆蛋白质组学分析（plasma proteomic analysis）显示，补体级联反应（complement cascade）抑制剂的水平显著升高，其中包括簇连蛋白（CLU），而该物质可增强跑步血浆的抗炎效应。经静脉注射的CLU可强力结合大脑内皮细胞（brain endothelial cells），在急性大脑炎症模型与阿尔茨海默病模型小鼠中，均可降低这些细胞的炎症基因表达水平。上述研究结果证实，可转移、靶向脑血管系统并改善大脑功能的抗炎“运动因子”确实存在。本研究旨在鉴定外源性簇连蛋白在急性（脂多糖（LPS））或慢性（淀粉样前体蛋白（APP））炎症两种小鼠模型中，对大脑内皮细胞所诱导的转录组（transcriptomic）变化。