Mota Bibiana C, Kelly Áine M
Department of Physiology, School of Medicine and Trinity College Institute of Neuroscience and Trinity Biomedical Sciences Institute, Trinity College Dublin, University of Dublin, Dublin, Ireland.
Neuronal Signal. 2020 Dec 2;4(4):NS20200003. doi: 10.1042/NS20200003. eCollection 2020 Dec.
Experimental and epidemiological evidence suggest that modifiable lifestyle factors, including physical exercise, can build structural and cognitive reserve in the brain, increasing resilience to injury and insult. Accordingly, exercise can reduce the increased expression of proinflammatory cytokines in the brain associated with ageing or experimentally induced neuroinflammation. However, the cellular mechanisms by which exercise exerts this effect are unknown, including the effects of exercise on classic or alternative activation of astrocytes and microglia. In the present study, we assess the effects of nine consecutive days of treadmill running on the glial cell response to a single systemic injection of lipopolysaccharide (LPS) and, in parallel, the effects on spatial learning and memory. We show that prior exercise protects against LPS-induced impairment of performance in the object displacement task concomitant with attenuation of IL-1β, TNFα and IL-10 mRNA expression in the hippocampus. Assessment of isolated astrocytes and microglia revealed that LPS induced a proinflammatory response in these cells that was not observed in cells prepared from the brains of mice who had undergone prior exercise. The results suggest that exercise modulates neuroinflammation by reducing the proinflammatory microglial response, suggesting a mechanism by which exercise may be neuroprotective.
实验和流行病学证据表明，包括体育锻炼在内的可改变生活方式因素能够在大脑中建立结构和认知储备，增强对损伤和损害的恢复力。因此，运动可以减少与衰老或实验性诱导的神经炎症相关的大脑中促炎细胞因子表达的增加。然而，运动发挥这种作用的细胞机制尚不清楚，包括运动对星形胶质细胞和小胶质细胞经典或替代性激活的影响。在本研究中，我们评估了连续九天在跑步机上跑步对胶质细胞对单次全身注射脂多糖（LPS）的反应的影响，同时评估其对空间学习和记忆的影响。我们发现，预先运动可防止LPS诱导的物体位移任务中的行为表现受损，同时海马体中IL-1β、TNFα和IL-10 mRNA表达也会减弱。对分离的星形胶质细胞和小胶质细胞的评估显示，LPS在这些细胞中诱导了促炎反应，而在预先运动小鼠的大脑中制备的细胞中未观察到这种反应。结果表明，运动通过减少促炎性小胶质细胞反应来调节神经炎症，这提示了运动可能具有神经保护作用的一种机制。
