身体活動関連細胞外小胞は炎症誘発性微小膠細胞活性化を阻害する

Excessive microglial activation and neuroinflammation are pivotal contributors to the progression of neurodegenerative diseases. Physical activity has emerged as a complementary therapy recognized for its anti-inflammatory effects. Long-term treadmill-induced mandatory physical activity (TMPA), a rodent paradigm modeling exercise with controllable intensity, has been shown to reduce age-related microglial activation, dopaminergic neuron degeneration in the substantia nigra, and motor impairments in mice. However, the mechanisms underlying these effects remain unclear. Given the role of physical activity-induced exerkines in modulating anti-inflammatory responses, this study investigated the effects of plasma-derived extracellular vesicles (EVs) from TMPA-treated animals on inflammagen-induced microglial activation in both in vitro and in vivo models. We showed that plasma from TMPA-treated rats suppressed lipopolysaccharide (LPS)-induced inflammatory signaling pathways in BV2 microglia cell line. Within 2 h, over 60% of BV2 microglia internalized EVs, and EVs from rats significantly inhibited LPS-induced microglial activation. In vivo, DiI-labeled EVs from TMPA-treated rats, delivered via tail vein injection, were detected in the brain parenchyma of recipient mice within one day. LPS-treated mice receiving EVs from TMPA-treated rats exhibited significantly lower microglial activation in the substantia nigra compared to those receiving EVs from sedentary rats. These findings demonstrate that physical activity-derived EVs effectively suppress inflammagen-induced microglial activation, providing new insights into their anti-neuroinflammatory properties and potential as therapeutic agents for neuroinflammation-related diseases.