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Exercise increases levels of anti-inflammatory factors that may have a protective effect on the brain, according to observations in mice reported in Nature this week. These factors improve learning and memory when transferred into non-exercising mice, and are shown to increase in a small group of patients with cognitive impairment who followed a 6-month exercise programme. The findings provide new insights into the mechanism of how physical exercise benefits the brain.

While beneficial effects of exercise on the brain and cognitive function have been universally recognized, the underlying mechanism is poorly understood. To determine whether exercise increases plasma levels of factors that may contribute to healthy brain function, Tony Wyss-Coray and colleagues collected plasma from sedentary mice and mice that had access to a running wheel for 28 days, and injected the plasma into young, non-exercising mice. The mice that received plasma from the running mice showed a notable increase of hippocampal cell proliferation and survival, which was similar to the direct effects of running observed in the exercising mice. Contextual and spatial learning and memory was also shown to be boosted in the mice that received plasma from the exercising mice. Using proteomic analysis of the plasma, the authors found that specific factors, such as a protein called clusterin, had crucial roles in the anti-inflammatory effects of exercise. Intravenously injected clusterin demonstrated anti-inflammatory effects in both an acute mouse model of brain inflammation and a mouse model of Alzheimer’s disease. The authors also observed an increase of plasma clusterin levels in 20 patients with mild cognitive impairment after a 6-month physical exercise intervention.

The findings demonstrate the potential existence of transferrable anti-inflammatory ‘exercise factors’ in plasma that benefit the brain, and provide new ideas for developing therapies to address diseases such as Alzheimer’s disease.