Microglial activation and neuroinflammatory changes are characteristic of the aged brain and contribute to age-related cognitive impairment. Exercise improves cognitive function in aged animals, perhaps because of a modulatory effect on microglial activation. Recent evidence indicates that inflammatory microglia are glycolytic, driven by an increase in 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3), an enzyme that is described as the master regulator of glycolysis. Here we investigated whether microglia from aged animals exhibited a glycolytic signature and whether exercise exerted a modulatory effect on this metabolic profile. Young (4 month-old) and aged (18 month-old) mice were trained for 10 days on a treadmill. One day before sacrifice, animals were assessed in the novel object recognition and the object displacement tests. Animals were sacrificed after the last bout of exercise, microglial cells were isolated, cultured for 5 days and assessed for metabolic profile. Performance in both behavioural tests was impaired in sedentary aged animals and exercise attenuated this age-related effect. A significant increase in glycolysis, glycolytic capacity and PFKFB3 was observed in microglia from aged animals and exercise ameliorated these effects, while it also increased the phagocytic capacity of cells. The senescent markers, β-galactosidase and p16INK4A, were increased in microglia from sedentary aged mice, and expression of these markers was significantly decreased by exercise. The data demonstrate that the exercise-related improved cognition is orchestrated by a normalization of the metabolic profile and functionality of microglia.

中文翻译：

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运动诱导的小胶质细胞与年龄相关的代谢变化的重新编程伴随着衰老细胞的减少

小胶质细胞激活和神经炎症变化是老年大脑的特征，并导致与年龄相关的认知障碍。运动可以改善老年动物的认知功能，这可能是由于对小胶质细胞活化的调节作用。最近的证据表明，炎症性小胶质细胞是糖酵解的，由 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) 的增加驱动，PFKFB3 是一种被描述为糖酵解主要调节剂的酶。在这里，我们研究了来自老年动物的小胶质细胞是否表现出糖酵解特征，以及运动是否对这种代谢特征产生调节作用。年轻（4 个月大）和老年（18 个月大）小鼠在跑步机上训练 10 天。在处死前一天，动物在新的物体识别和物体位移测试中进行了评估。最后一次运动后处死动物，分离小胶质细胞，培养5天并评估代谢情况。久坐的老年动物在两种行为测试中的表现都受到损害，运动减弱了这种与年龄相关的影响。在老年动物的小胶质细胞中观察到糖酵解、糖酵解能力和 PFKFB3 显着增加，运动改善了这些影响，同时也增加了细胞的吞噬能力。久坐不动的老年小鼠的小胶质细胞中的衰老标志物 β-半乳糖苷酶和 p16INK4A 增加，而这些标志物的表达因运动而显着降低。数据表明，与运动相关的认知改善是通过小胶质细胞的代谢特征和功能的正常化来协调的。