Athinoula A Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, United States.
Neuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, United States.
Elife. 2023 Jul 4;12:e86329. doi: 10.7554/eLife.86329.
Aging is a major risk factor for cognitive impairment. Aerobic exercise benefits brain function and may promote cognitive health in older adults. However, underlying biological mechanisms across cerebral gray and white matter are poorly understood. Selective vulnerability of the white matter to small vessel disease and a link between white matter health and cognitive function suggests a potential role for responses in deep cerebral microcirculation. Here, we tested whether aerobic exercise modulates cerebral microcirculatory changes induced by aging. To this end, we carried out a comprehensive quantitative examination of changes in cerebral microvascular physiology in cortical gray and subcortical white matter in mice (3-6 vs. 19-21 months old), and asked whether and how exercise may rescue age-induced deficits. In the sedentary group, aging caused a more severe decline in cerebral microvascular perfusion and oxygenation in deep (infragranular) cortical layers and subcortical white matter compared with superficial (supragranular) cortical layers. Five months of voluntary aerobic exercise partly renormalized microvascular perfusion and oxygenation in aged mice in a depth-dependent manner, and brought these spatial distributions closer to those of young adult sedentary mice. These microcirculatory effects were accompanied by an improvement in cognitive function. Our work demonstrates the selective vulnerability of the deep cortex and subcortical white matter to aging-induced decline in microcirculation, as well as the responsiveness of these regions to aerobic exercise.
衰老是认知障碍的一个主要危险因素。有氧运动有益于大脑功能，并可能促进老年人的认知健康。然而，大脑灰质和白质的潜在生物学机制仍不清楚。白质对小血管疾病的选择性易损性以及白质健康与认知功能之间的联系表明，深部脑微循环的反应可能具有潜在作用。在这里，我们测试了有氧运动是否能调节衰老引起的大脑微循环变化。为此，我们对 3-6 个月和 19-21 个月大的小鼠大脑皮质灰质和皮质下白质的脑血管生理学变化进行了全面的定量检查，并询问了运动是否以及如何能挽救年龄引起的缺陷。在久坐组中，与皮质浅层（颗粒层上）相比，衰老导致大脑深（颗粒层下）皮质层和皮质下白质的微血管灌注和氧合更严重下降。5 个月的自愿有氧运动以深度依赖的方式部分恢复了老年小鼠的微血管灌注和氧合，并使这些空间分布更接近年轻成年久坐小鼠。这些微循环效应伴随着认知功能的改善。我们的工作表明，深部皮质和皮质下白质对白质老化引起的微循环下降具有选择性易损性，以及这些区域对有氧运动的反应性。
