Voluntary running exercise after focal cerebral ischemia modifies astrocytic population and features

Voluntary running exercise after focal cerebral ischemia promotes functional recovery and prevents the ischemia-induced dendritic spine loss in the peri-infarct motor cortex layer 5. Neuronal morphology is affected by the perineuronal environmental change. Glia exert crucial roles in the formation of perineuronal environment, and exercise-induced changes of glial phenotype are expected. Here, we demonstrated that voluntary running exercise increased the population of newborn astrocytes in the acute phase after cerebral ischemia at late phase. Transcriptome analysis detected 10 upregulated genes and 70 downregulated genes by exercise in the ipsilateral cortex astrocytes. Gene cluster downregulated by exercise were significantly associated with neuronal morphology. The expression of Lipocalin 2, a factor of decreasing dendritic spines, tended to be decreased in the postischemic astrocytes by exercise. Our results suggest that exercise modifies the phenotype of postischemic astrocytes, which relate to the exercise-induced amelioration of postischemic dendritic spine loss. To induce permanent focal cerebral ischemia, middle cerebral artery occlusion (MCAO) was performed for seven-weeks old male C.B-17/Icr-+/+Jcl mice. Mice were divided into MCAO + non-exercise group and MCAO + exercise group. MCAO + exercise group mice were exposed to running wheel after MCAO for voluntary exercise for 15 days. To detect the newborn cells after cerebral ischemia, 5-bromo-2’-deoxyuridine (BrdU) was administered to each group through intraperitoneal injection with a dose of 50 mg/kg/day at postoperative day (POD) 0 (immediately after MCAO), 1, 2 and 3. Transcriptome of postischemic astrocytes were compared between MCAO + non-exercise group and MCAO + exercise group at POD15 by sorting ACSA-2-positive astrocytes from the ipsilateral cortices.