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[耐力运动对老年大鼠大脑皮质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].

作者信息

Liu Wen-Feng, Liu Shao-Peng, Fu Rang, Wang Zhi-Yuan, Kuang He-Yu, Xia Yan, Tang Chang-Fa

机构信息

Hunan Provincial Key Laboratory of Physical Fitness and Sports Rehabilitation, Hunan Normal University, Changsha 410012, China.

出版信息

Zhongguo Ying Yong Sheng Li Xue Za Zhi. 2019 Jul 28;35(4):339-345. doi: 10.12047/j.cjap.5803.2019.072.

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) 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 Ca/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.

摘要

目的

了解并分析耐力运动对老年大鼠大脑皮质适应性机制的影响规律。

方法

本研究选取3月龄(n = 20)、13月龄(n = 24)和23月龄(n = 24)的无特定病原体(SPF)雄性斯普拉格-道利大鼠(SD大鼠),分为青年(Y-SED)、中年(M-SED)和老年(O-SED)久坐对照组,以及相应的耐力运动跑步组Y-EX、M-EX和O-EX。对耐力运动跑步组进行为期10周的常规中等强度有氧运动干预。运动方式为跑步机运动(坡度0),运动强度从最大耗氧量(V·O)的60%~65%逐渐增加至70%~75%,运动时间为10周。采用苏木精-伊红(HE)染色检测与年龄相关的形态学变化。检测超氧化物歧化酶(SOD)、脑源性神经营养因子(BDNF)的表达,以及突触素1(SYN1)和钙/钙调蛋白依赖性蛋白激酶IIα(CaMK IIα)/AMP激活蛋白激酶α1(AMPKα1)/雷帕霉素靶蛋白(mTOR)通路相关基因的表达。

结果

各组大鼠大脑皮质结构均呈现与年龄相关的老化改变,皮质中SOD表达呈逐渐下降趋势,BDNF表达呈随年龄增加的趋势,SYN1和CaMK IIα表达水平随年龄增加。中年大鼠AMPKα1、SirT2及IP3R、AKT1和mTOR mRNA水平变化略有增加,老年大鼠则下降。与各久坐对照组大鼠相比,各运动组大鼠大脑皮质细胞核排列紧密,显微镜下观察到的细胞核数量显著增加。运动促进了大鼠皮质中SOD、BDNF和突触素SYN1的表达,老年大鼠SOD和BDNF表达水平显著上调(P<0.01)。SYN1在青年和老年大鼠中的表达水平显著上调(P<0.05)。中年和老年大鼠皮质中CaMK IIα表达上调(P<0.01),而青年大鼠中CaMK IIα表达水平下调(P<0.01)。运动可上调青年大鼠皮质中AMPKα1表达水平(P<0.05),但对中年和老年大鼠无此作用。运动可上调各年龄组大鼠皮质中SirT2表达(P<0.05)。运动上调了大鼠皮质中磷酸肌醇3激酶(IP3R)/蛋白激酶B 1(AKT1)/mTOR的表达,其中青年组青年IP3R显著上调(P<0.01),青年和中年组mTOR显著上调(P<0.01),老年组mTOR也显著上调(P<0.05)。

结论

耐力运动上调BDNF表达,调节CaMKIIα信号,激活AMPK信号通路和IP3R/AKT1/mTOR信号通路,改善皮质突触可塑性。

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