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Timing-Dependent Protection of Swimming Exercise against d-Galactose-Induced Aging-Like Impairments in Spatial Learning/Memory in Rats

by Xue Li 1,2, Lu Wang 2, Shuling Zhang 2, Xiang Hu 2, Huijun Yang 3,* and Lei Xi 4
Department of Human Anatomy, West China School of Preclinical and Forensic Medical Institute, Sichuan University, Chengdu 610041, China
Department of Human Kinesiology, School of Sports Medicine and Health, Chengdu Sport University, Chengdu 610041, China
Department of Morphology Laboratory, Chengdu Medical College, Chengdu 610083, China
Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA 23298-0204, USA
Author to whom correspondence should be addressed.
Brain Sci. 2019, 9(9), 236;
Received: 23 July 2019 / Revised: 2 September 2019 / Accepted: 11 September 2019 / Published: 14 September 2019
(This article belongs to the Special Issue Exercising against Age-Effects on the Brain)
This study was designed to investigate beneficial effects of swimming exercise training on learning/memory, synaptic plasticity and CREB (cAMP response element binding protein) expression in hippocampus in a rat model of d-galactose-induced aging (DGA). Eighty adult male rats were randomly divided into four groups: Saline Control (group C), DGA (group A), Swimming exercise before DGA (group S1), and Swimming during DGA (group S2). These four groups of animals were further divided into Morris water maze training group (M subgroup) and sedentary control group (N subgroup). Spatial learning/memory was tested using Morris water maze training. The number and density of synaptophysin (Syp) and metabotropic glutamate receptor 1 (mGluR1) in hippocampal dentate gyrus area, CREB mRNA and protein expression and DNA methylation levels were determined respectively with immunohistochemistry, western blot, real-time PCR, and MassArray methylation detection platform. We found that compared with group C, DGA rats showed aging-like poor health and weight loss as well as hippocampal neurodegenerative characteristics. Exercise training led to a time-dependent decrease in average escape latency and improved spatial memory. Exercise training group (S2M) had significantly increased swim distance as compared with controls. These functional improvements in S2M group were associated with higher Syp and mGluR1 values in hippocampus (p < 0.01) as well as higher levels of hippocampal CREB protein/mRNA expression and gene methylation. In conclusion, swimming exercise training selectively during drug-induced aging process protected hippocampal neurons against DGA-elicited degenerative changes and in turn maintained neuronal synaptic plasticity and learning/memory function, possibly through upregulation of hippocampal CREB protein/mRNA and reduction of DGA-induced methylation of CREB. View Full-Text
Keywords: aging; exercise; hippocampus; learning; memory; neurodegeneration; neuroprotection aging; exercise; hippocampus; learning; memory; neurodegeneration; neuroprotection
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Li, X.; Wang, L.; Zhang, S.; Hu, X.; Yang, H.; Xi, L. Timing-Dependent Protection of Swimming Exercise against d-Galactose-Induced Aging-Like Impairments in Spatial Learning/Memory in Rats. Brain Sci. 2019, 9, 236.

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