Exercise conditioned plasma dampens inflammation via clusterin and boosts memory > NEWS

Physical activity evokes profound physiological responses in multiple tissues in species from fish, to birds, rats, mice and humans 1–6. It is widely accepted and promoted as a method of improving human health, including brain health 7–9. Exercise interventions in people of various ages with or without neurodegenerative diseases, or brain damage, have been shown to improve cognitive function 9,10,11,12. Neuroinflammation is a common feature of these conditions and potential mediator of the cognitive impairment associated with them 13–16. Studies in mouse models of aging and neurodegenerative diseases, such as AD and Parkinson disease have linked long-term voluntary wheel running with improved learning and memory, and decreased neuroinflammation 17–20. However, how exercise exerts these beneficial effects on the brain is poorly understood. It is possible that the physical exertion of muscle or lung during exercise may result in the secretion of factors from these or other tissues which subsequently signal to the brain to reduce neuroinflammation. Indeed, physical exercise increases levels of dozens of proteins in plasma, many of which are likely released from muscle tissue and thus named myokines 2,21. Some of these myokines, such as insulin-like growth factor-1 (IGF-1) 22, vascular endothelial growth factor (VEGF) 23 and platelet factor 4 (PF4) 24 increase following exercise and have been shown to increase hippocampal neurogenesis (Extended Table 1). However, it is unknown whether exercise conditioned plasma contains the factors benefitting the brain, whether these factors are directly transferrable through plasma, how such factors impact the brain, and what the key factors are.