Abstract:
Physical exercise reduces the effects of aging and cognitive decline by improving synaptic plasticity and spatial learning. However, the underlying neurobiological mechanisms are unclear. A total of 45 Male SPF Sprague-Dawley rats were acclimatized and then allocated into three groups, 15 in each group: the saline control (DC) group, D-gal-induced aging (DA) group, and D-gal-induced aging + exercise (DE) group. Six weeks of intraperitoneal injections of D-gal at a concentration of 100 mg/kg body weight/d was injected to establish model of aging in the DA and DE groups. Morris water maze test was implemented to evaluate the hippocampus related cognition. SOD activity and MDA was tested to assess the aging in all groups. H&E and Nissl staining was used to observe the histopathological changes of hippocampal neurons in aging rats. Quantitative real-time polymerase chain reaction, western blotting and immunofluorescence staining techniques were used to investigate the expression of synaptic genes and proteins in the hippocampus. Massarray methylation system was employed to measure the PDE-4 gene methylation level in rat hippocampal tissues. Our results demonstrated that exercise intervention improves cognitive function in D-gal-induced aging rats. The methylation of CpG sites in PDE-4 in the hippocampus was significantly increased. The physical exercise significantly increased PDE-4 gene methylation and effectively decreased PDE-4 gene and protein expression. These beneficial behavioral and morphological effects were attributed to PDE-4 methylation, which was activated cAMP/PKA/CREB pathway and improved synaptic plasticity. Exercise induced PDE-4 methylation is key mechanism underpinning the amelioration of learning/memory impairment, suggesting the potential efficacy of physical exercise training in delaying brain aging.
摘要:
体育锻炼通过改善突触可塑性和空间学习来减少衰老和认知能力下降的影响。然而,潜在的神经生物学机制尚不清楚.使45只雄性SPFSprague-Dawley大鼠适应环境,然后分为三组,每组15:生理盐水对照组(DC),D-半乳糖致衰老(DA)组,D-gal诱导衰老+运动(DE)组。DA组和DE组腹腔注射浓度为100mg/kg体重/d的D-gal6周,建立衰老模型。采用Morris水迷宫试验评价海马相关认知功能。测定各组的SOD活性和MDA来评价衰老。采用H&E和Nissl染色观察衰老大鼠海马神经元的组织病理学改变。定量实时聚合酶链反应,免疫印迹和免疫荧光染色技术用于研究海马突触基因和蛋白的表达。Massarray甲基化系统用于测量大鼠海马组织中PDE-4基因的甲基化水平。我们的结果表明,运动干预可以改善D-gal诱导的衰老大鼠的认知功能。海马PDE-4中CpG位点的甲基化明显增加。体育锻炼可显著增加PDE-4基因的甲基化,有效降低PDE-4基因和蛋白的表达。这些有益的行为和形态效应归因于PDE-4甲基化,激活了cAMP/PKA/CREB通路,提高了突触可塑性。运动诱导的PDE-4甲基化是改善学习/记忆障碍的关键机制,表明体育锻炼对延缓大脑衰老的潜在功效。