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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Department of Exercise Physiology, Beijing Sport University, Beijing, China.
Yan
Y
Li
Department of Exercise Physiology, Beijing Sport University, Beijing, China.
Li
L
Zhao
Key Laboratory of Physical Fitness and Exercise, Ministry of Education, Beijing Sport University, Beijing, China.
Boya
B
Gu
Department of Exercise Physiology, Beijing Sport University, Beijing, China.
Jiajia
J
Cai
Key Laboratory of Physical Fitness and Exercise, Ministry of Education, Beijing Sport University, Beijing, China.
Yuanyuan
Y
Lv
Department of Exercise Physiology, Beijing Sport University, Beijing, China.
Laikang
L
Yu
D051339:Actin Depolymerizing Factors / Q000032:analysis / Q000502:physiology; D000375:Aging / Q000502:physiology*; D000818:Animals; D015153:Blotting, Western; D002540:Cerebral Cortex / Q000737:chemistry / Q000502:physiology; D005455:Fluorescent Antibody Technique; D006624:Hippocampus / Q000737:chemistry / Q000502:physiology; D008297:Male; D010805:Physical Conditioning, Animal / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000502:physiology*; D013569:Synapses / Q000502:physiology*; D020764:cdc42 GTP-Binding Protein / Q000032:analysis / Q000502:physiology; D020830:rac1 GTP-Binding Protein / Q000032:analysis / Q000502:physiology*; D020742:rhoA GTP-Binding Protein / Q000032:analysis / Q000502:physiology*
D051339:Actin Depolymerizing Factors; D020764:cdc42 GTP-Binding Protein; D020830:rac1 GTP-Binding Protein; D020742:rhoA GTP-Binding Protein