Running Promotes Transformation of Brain Astrocytes Into Neuroprotective Reactive Astrocytes and Synaptic Formation by Targeting Gpc6 Through the STAT3 Pathway

Ischemic stroke is caused by cerebral ischemia upon the blockage of an artery, which results in a high disability rate. Little is known regarding the mechanism of astrocyte function in cerebral ischemia. We aimed to determine the effects of running on the transformation of astrocytes, and subsequent synapse formation. A study of middle cerebral artery occlusion (MCAO) after running in vivo showed that running can promote the transformation of astrocytes toward the neuroprotective phenotype. Our findings of oxygen-glucose deprived astrocytes in vitro after running revealed that these astrocytes transformed into the neuroprotective phenotype, and that the expression of STAT3 and Gpc6 was increased. We confirmed that mechanistically, running can target Gpc6 through the STAT3 pathway and then regulate the number of synapses. We concluded that running promotes synapse proliferation by polarizing astrocytes toward the neuroprotective phenotype and ultimately leads to nerve regeneration.