reversal of glial and neurovascular markers of unhealthy brain aging by exercise in middle-aged female mice逆转的胶质和运动神经与血管的标记不健康的大脑衰老的中年雌性老鼠.pdfVIP

Reversal of Glial and Neurovascular Markers of Unhealthy Brain Aging by Exercise in Middle-Aged Female Mice ¤ ´ Caitlin S. Latimer, James L. Searcy , Michael T. Bridges, Lawrence D. Brewer, Jelena Popovic, Eric M. Blalock, Philip W. Landfield, Olivier Thibault, Nada M. Porter* Department of Molecular and Biomedical Pharmacology, University of Kentucky College of Medicine, Lexington, Kentucky, United States of America Abstract Healthy brain aging and cognitive function are promoted by exercise. The benefits of exercise are attributed to several mechanisms, many which highlight its neuroprotective role via actions that enhance neurogenesis, neuronal morphology and/or neurotrophin release. However, the brain is also composed of glial and vascular elements, and comparatively less is known regarding the effects of exercise on these components in the aging brain. Here, we show that aerobic exercise at mid-age decreased markers of unhealthy brain aging including astrocyte hypertrophy, a hallmark of brain aging. Middle- aged female mice were assigned to a sedentary group or provided a running wheel for six weeks. Exercise decreased hippocampal astrocyte and myelin markers of aging but increased VEGF, a marker of angiogenesis. Brain vascular casts revealed exercise-induced structural modifications associated with improved endothelial function in the periphery. Our results suggest that age-related astrocyte hypertrophy/reactivity and myelin dysregulation are aggravated by a sedentary lifestyle and accompanying reductions in vascular function. However, these effects appear reversible with exercise initiated at mid-age. As this period of the lifespan coincides with the appearance of multiple ma