Physical Fitness Influences Brain Health in Part via Effects on Microglia

Microglia are innate immune cells resident in the central nervous system, analogous to macrophages elsewhere in the body, but with an extended portfolio of activities that include assisting in management of synaptic connections between neurons. In recent years, researchers have placed an ever greater focus on the behavior of microglia, particularly their contribution to chronic inflammatory signaling in the brain, in the context of aging and neurodegenerative disease. Aging is characterized by overly active inflammatory microglia and greater numbers of senescent microglia. Ways to clear and regenerate the microglial population, or otherwise change their behavior for the better, have shown some promise in animal models. Here, researchers review the evidence for some of the benefits of physical fitness, improved cognitive function and slowed cognitive aging, to be mediated by favorable changes in the behavior of microglia.

It is largely accepted that physical exercise (PE) can promote brain health and cognitive function. Reports in humans show that moderate to vigorous PE can enhance cognition. However, the cellular mechanisms that underlie this phenomenon are still an active area of exploration. Traditionally, studies have examined how PE regulates wiring of neuronal connections to enhance cognitive function. However, recent focus has shifted toward how exercise may regulate inflammation and the immune response in the central nervous system (CNS).

Microglia are the resident immune cells of the CNS responsible for mediating inflammatory responses, tissue maintenance, and synapse remodeling. Microglia are key mediators of neuroinflammatory processes and play a role in maintaining brain homeostasis in healthy and pathological settings. Here, we explore the evidence suggesting that physical activity has the potential to regulate microglia activity in various animal models. We emphasize key areas where future research could contribute to uncovering the therapeutic benefits of engaging in physical exercise.