Abstract
PurposeThe role of exercise to prevent or reverse aging-induced cognitive decline has been widely reported. This neuroprotection is associated with changes in the synaptic structure plasticity. However, the mechanisms of exercise-induced synaptic plasticity in the aging brain are still unclear. Thus, the aim of the present study is to investigate the aging-related alterations of Rho-GTPase and the modulatory influences of exercise training.MethodsYoung and old rats were used in this study. Old rats were subjected to different schedules of aerobic exercise (12 m/min, 60 min/d, 3d/w or 5d/w) or kept sedentary for 12 w. After 12 w of aerobic exercise, the synapse density in the cortex and hippocampus was detected with immunofluorescent staining using synaptophysin as a marker. The total protein levels of RhoA, Rac1, Cdc42 and cofilin in the cortex and hippocampus were detected with Western Blot. The activities of RhoA, Rac1 and Cdc42 were determined using a pull down assay.ResultsWe found that synapse loss occurred in aging rats. However, the change of expression and activity of RhoA, Rac1 and Cdc42 was different in the cortex and hippocampus. In the cortex, the expression and activity of Rac1 and Cdc42 was greatly increased with aging, whereas there were no changes in the expression and activity of RhoA. In the hippocampus, the expression and activity of Rac1 and Cdc42 was greatly decreased and there were no changes in the expression and activity of RhoA. As a major downstream substrate of the Rho GTPase family, the increased expression of cofilin was only observed in the cortex. High frequency exercise ameliorated all aging-related changes in the cortex and hippocampus.ConclusionsThese data suggest that aerobic exercise reverses synapse loss in the cortex and hippocampus in aging rats, which might be related to the regulation of Rho GTPases.
Highlights
As aging occurs and the mean life expectancy extends, the “normal” aging process is often associated with specific impairments in both learning and memory
We found that synapse loss occurred in aging rats
High frequency exercise ameliorated all aging-related changes in the cortex and hippocampus. These data suggest that aerobic exercise reverses synapse loss in the cortex and hippocampus in aging rats, which might be related to the regulation of Rho GTPases
Summary
As aging occurs and the mean life expectancy extends, the “normal” aging process is often associated with specific impairments in both learning and memory. Electron microscopy studies have shown a substantial synapse loss in the prefrontal cortex of aged rhesus monkeys [2, 3]. The factors driving these alterations are still obscure. Cofilin is one of the major actin depolymerization factor (actin-binding protein) in the brain and severs filamentous actin (F-actin) into short segments and creates free barbed ends for actin elongation [10], which plays a critical role in neurite growth and growth cone turning [2, 3, 11], receptor trafficking [12], and dendritic spinogenesis and synaptic plasticity [13, 14]. Misregulation of neuronal actin and cofilin is associated with a range of cognitive impairment and degenerative condition [15]
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