耐力运动对增龄大鼠脑皮层突触可塑性的影响及相关调控机制*

doi:10.12047/j.cjap.5803.2019.072

摘要/Abstract

摘要： 目的:探讨规律性耐力运动对脑皮层增龄性老化适应性的作用与机制。方法:将三个不同年龄段的健康SPF级雄性Sprague-Dawley大鼠分为3月龄 (青年,n=20)、13月龄 (中年,n=24)和23月龄 (老年,n=24)组,每组又随机分为静息组和运动组;静息组三组静息,运动组三组实施10周递增负荷规律的中等强度耐力运动:运动方式为跑台运动(坡度0),运动强度从最大摄氧量(V·O2max) 60%～65%逐渐递增到70%～75%,运动时间为10周;取大鼠脑皮层,HE染色测试大鼠脑皮层增龄性形态学变化,检测BDNF和SOD的蛋白表达及突触素-1(SYN1)和CaMK IIα/AMPKα1/ mTOR通路等相关基因。结果:静息各组大鼠的脑皮层结构呈现年龄增龄性衰老变化,脑皮层SOD表达呈增龄性下降趋势,BDNF表达变化呈增龄性上升趋势,SYN1和CaMK IIα表达水平随增龄性趋势变化不大,AMPKα1和SirT2以及 IP3R、AKT1、mTOR mRNA表达水平随年龄变化呈现中年略上升而老年下降趋势;与静息各组大鼠相比,运动各组大鼠脑皮层神经细胞核排列紧密有序,显微镜下观察细胞核的数量明显增加,运动促进大鼠脑皮层SOD、BDNF和突触素SYN1表达水平增加,其中老年大鼠SOD、BDNF表达水平显著上调(P＜0.01),青年和老年大鼠SYN1表达水平显著上调(P＜0.05),运动上调中年和老年大鼠脑皮层CaMK IIα表达水平上调(P＜0.01),而对青年大鼠CaMK IIα表达水平却是下调(P＜0.01),运动可上调青年大鼠脑皮层的AMPKα1表达水平(P＜0.05),而对中年和老年大鼠AMPKα1的影响不显著,运动均可上调各年龄大鼠脑皮层的SirT2表达水平(P＜0.05),运动上调各年龄大鼠脑皮层的IP3R/AKT1/ mTOR表达水平,其中青年IP3R显著上调(P＜0.01),青年和中年mTOR显著上调(P＜0.01),老年mTOR也显著上调(P＜0.05)。结论:耐力运动通过上调BDNF的表达水平,调控CaMK IIα信号、激活AMPK信号通路和IP3R/AKT1/mTOR信号通路,改善脑皮层的突触可塑性。

关键词: 大鼠, 耐力运动, 突触可塑性, 增龄性老化, 突触素-1, CaMK IIα/AMPKα1/ mTOR信号通路

Abstract: Objective: To understand and analyze the rules of endurance exercise on the cerebral cortex adaptive mechanism in aged rats. Methods: In this study, 3-month-old (n=20), 13-month-old (n=24) and 23-month-old (n=24) specific-pathogen free (SPF) male Sprague-Dawley Rat (SD) rats were divided into young (Y-SED), middle-aged (M-SED) and old-aged (O-SED) sedentary control group, and the corresponding Y-EX, M-EX and O-EX in the endurance exercise runner group. The 10-weeks of regular moderate-intensity aerobic exercise intervention were carried out in the endurance exercise runner group. The exercise mode is treadmill exercise (slope 0), and the exercise intensity gradually increases from 60%～65% of the maximum oxygen consumption (V·O_2max) to 70%～75%, and the exercise time is 10 weeks. Hematoxylin and eosin (HE) staining was used to detect age-related morphological changes. The expressions of superoxide dismutase(SOD) and brain-derived neurotrophic factor (BDNF) and the expressions of synapsin 1 (SYN1) and Ca²⁺/calmodulin- dependent protein kinases IIα (CaMK IIα) / AMP-activated protein kinase α1(AMPKα1) / mammalian target of rapamycin (mTOR) pathway -related genes were detected. Results: The cerebral cortex structure of the rats in each group showed age-related aging changes, the expression of SOD in the cortex showed a gradual decline, the expression of BDNF showed an age-increasing trend, and the expression levels of SYN1 and CaMK IIα were increased with age. The changes in AMPKα1 and SirT2 and IP3R, AKT1 and mTOR mRNA levels were increased slightly in middle-aged rats and decreased in aged rats. Compared with the rats in each sedentary control group, the nucleus of the cerebral cortex was tightly arranged and the number of nuclei observed under the microscope was increased significantly in each exercise group. Exercise promoted the expressions of SOD, BDNF and synaptophysin SYN1 in the cortex of rats, and the expression levels of SOD and BDNF in aged rats were up-regulated significantly (P＜ 0.01). The expression level of SYN1 in rats was up-regulated significantly (P＜0.05) in the young and aged rats. The expression of CaMK IIα in the cortex of middle-aged and aged rats was up-regulated (P＜0.01), while the expression level of CaMK IIα in young rats was down-regulated (P＜0.01). Exercise could up-regulate the expression level of AMPKα1 in the cortex of young rats (P＜ 0.05), but not in middle-aged and old-age rats. Exercise could up-regulate the expression of SirT2 in the cortex of rats in all age groups (P＜0.05). Exercise up-regulated the expression of phosphoinositide 3-kinase (IP3R)/ protein kinase B 1(AKT1) /mTOR in the cortex of rats, among which young IP3R was significantly up-regulated (P＜0.01) in the young group, mTOR was significantly up-regulated in young and middle-aged group (P＜0.01), and mTOR was also significantly up-regulated in the aged group (P＜0.05). Conclusion: Endurance exercise up-regulates BDNF expression, regulates CaMKIIα signaling, activates AMPK signaling pathway and IP3R / AKT1 / mTOR signaling pathway, and improves synaptic plasticity in the cortex.

Key words: rat, endurance exercise, synaptic plasticity, age-related aging, synapsin I, CaMK II&alpha, / AMPKα1 / mTOR signaling pathway

刘文锋, 刘少鹏, 傅让, 王志源, 旷何玉, 夏艳, 汤长发. 耐力运动对增龄大鼠脑皮层突触可塑性的影响及相关调控机制^*[J]. 中国应用生理学杂志, 2019, 35(4): 339-345.

LIU Wen-feng, LIU Shao-peng, FU Rang, WANG Zhi-yuan, KUANG He-yu, XIA Yan, TANG Chang-fa. Effects of endurance exercise on synaptic plasticity in cerebral cortex of aged rats and related regulatory mechanism[J]. CJAP, 2019, 35(4): 339-345.

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耐力运动对增龄大鼠脑皮层突触可塑性的影响及相关调控机制^*

Effects of endurance exercise on synaptic plasticity in cerebral cortex of aged rats and related regulatory mechanism

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