LAUSR

&NA; Exercise improves cognitive impairments induced by transient cerebral ischemia, and modulates synaptic adhesion molecules. In this study, we investigated effects of long‐term treadmill exercise on cognitive impairments and its relation to changes of synaptic cell adhesion molecule (SynCAM) 1/2/3 in the hippocampus after 5 min of transient cerebral ischemia in aged gerbils. Animals were assigned to sedentary and exercised groups, given treadmill exercise for 4 consecutive weeks from 5 days after transient ischemia, and evaluated cognitive function through passive avoidance test and Morris water maze test. SynCAM 2 protein levels were determined in the hippocampus by western blot. In addition, neuronal and synaptic changes were examined by NeuN immunohistochemistry, and SynCAM 1/2/3 and MAP2 double immunofluorescence, respectively. We found that transient cerebral ischemia led to neuronal death in the CA1 area and dentate gyrus, and impaired ‐memory function; however, 4 weeks of treadmill exercise improved ischemia‐induced memory impairment. In addition, SynCAM 1/2/3 and SynCAM 2 expression in the hippocampus was significantly decreased in the sedentary group after transient cerebral ischemia; however, SynCAM 1/2/3 expressionand and SynCAM 2 protein level was significantly increased in the ischemic group with exercise. These results suggest that long‐term treadmill exercise improves memory impairment through the restoration of decreased SynCAM 1/2/3 expression in the hippocampus induced by transient cerebral ischemia in the aged gerbil. HighlightsMemory was impaired following transient cerebral ischemiaLong‐term treadmill exercise improved ischemia‐induced memory impairment.Transient cerebral ischemia induced neuronal loss in the CA1 area of the hippocampus.Transient cerebral ischemia induced SynCAM reduction in the all hippocampal subregions.Treadmill exercise restored ischemia‐induced memory deficits by improving SynCAM