Journal Article

Aerobic exercise regulates Rho/cofilin pathways to rescue synaptic loss in aged rats

Cai, Jiajia, Gu, Boya, Lv, Yuanyuan, Zhao, Li, Li, Yan, Yu, Laikang

2017

Overview

The 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. Young 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. We 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. 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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Actin Depolymerizing Factors - analysis / Actin Depolymerizing Factors - physiology / Aerobic exercises / Aerobics / Aging / Aging (artificial) / Aging - physiology / Alzheimer's disease / Alzheimers disease / Animal cognition / Animals / Binding proteins / Biology and Life Sciences / Blotting, Western / Brain / Care and treatment / cdc42 GTP-Binding Protein - analysis / cdc42 GTP-Binding Protein - physiology / Cdc42 protein / Cerebral Cortex - chemistry / Cerebral Cortex - physiology / Cofilin / Cognitive ability / Cognitive disorders / Electron microscopy / Exercise physiology / Fitness equipment / Fitness training programs / Fluorescent Antibody Technique / Gene expression / Gerontology / Guanine nucleotide-binding protein / Guanosine triphosphatases / Guanosinetriphosphatase / Health aspects / Hippocampus / Hippocampus - chemistry / Hippocampus - physiology / Kinases / Laboratory animals / Male / Medicine and Health Sciences / Memory / Neurogenesis / Neurons / Neurophysiology / Neuroprotection / Neurosciences / Physical Conditioning, Animal - physiology / Physical fitness / Physical training / Plasticity / Polymerization / Proteins / rac1 GTP-Binding Protein - analysis / rac1 GTP-Binding Protein - physiology / Rac1 protein / Rats / Rats, Wistar / rhoA GTP-Binding Protein - analysis / rhoA GTP-Binding Protein - physiology / RhoA protein / Rodents / Running / Schedules / Signal Transduction - physiology / Substrates / Synapses / Synapses - physiology / Synaptic density / Synaptic plasticity / Synaptophysin