跑轮运动对小鼠皮质神经元AKT/mTOR通路活性及运动诱发电位的影响

doi:10.3969/j.issn.1674-8115.2021.10.002

摘要/Abstract

摘要：

目的·观察不同强度的跑轮运动对小鼠皮质神经元蛋白激酶B/哺乳动物雷帕霉素靶蛋白（protein kinase B/mammalian target of rapamycin，PKB/mTOR，AKT/mTOR）通路的激活情况及对神经传导的影响。方法·选取24只成年C57BL/6J小鼠为研究对象，随机分为对照组、低运动强度（low exercise intensity，LEI）组、中等运动强度（moderate exercise intensity，MEI）组和高运动强度（high exercise intensity，HEI）组，每组6只。4组小鼠接受为期3 d的预训练，结束后分别行不同强度的正式训练（1周）。检测运动诱发电位（motor-evoked potential，MEP）观察小鼠右上肢的神经传导情况。采用蛋白质印迹（Western blotting）检测小鼠运动皮质中AKT、核糖体蛋白S6（ribosomal S6 protein，S6）、胰岛素样生长因子1（insulin-like growth factor 1，IGF1）和脑源性生长因子（brain-derived neurotrophic factor，BDNF）表达情况。结果·MEP检测显示，与对照组相比，LEI组、MEI组和HEI组小鼠MEP的N1潜伏期有所缩短（均P<0.05）；与HEI组相比，LEI组小鼠的N1潜伏期更短（P=0.032）。同时，与对照组相比，LEI组小鼠MEP的P1潜伏期亦有缩短（P=0.015）。Western blotting结果显示，与对照组相比，LEI组、MEI组和HEI组小鼠运动皮质中p-AKT/AKT和p-S6/S6的表达水平明显升高（均P<0.05）；LEI组小鼠运动皮质中IGF1、BDNF的表达水平较对照组有所增加（均P<0.05）。结论·低强度运动训练能有效激活皮质神经元AKT/mTOR通路，提高神经传导速度，这可能与升高的神经生长因子水平相关。

关键词: 训练强度, 蛋白激酶B/哺乳动物雷帕霉素靶蛋白信号通路, 神经传导, 生长因子, 皮质神经元

Abstract:

Objective·To investigate the effects of various wheel-running exercise intensity on activation of protein kinase B/mammalian target of rapamycin (PKB/mTOR, AKT/mTOR) pathway in cortical neurons and nerve conduction in mice.

Methods·Twenty four adult C57BL/6J mice were randomly divided into control group, low exercise intensity (LEI) group, moderate exercise intensity (MEI) group and high exercise intensity (HEI) group, with 6 mice in each group. The four groups of mice received pre-training for 3 days, and then received formal training (1 week) with different intensity. Motor-evoked potential (MEP) was used to detect the nerve conduction in the right upper limb of mice. The expression of AKT, ribosomal S6 protein (S6), insulin-like growth factor 1 (IGF1) and brain-derived growth factor (BDNF) in the motor cortex of mice were detected by Western blotting.

Results·MEP test showed that compared with the control group, the N1 latency period of MEP in the LEI group, MEI Group and HEI group was shorter (all P<0.05); compared with the HEI group, the N1 latency period in the LEI group was shorter (P=0.032). Meanwhile, compared with the control group, the P1 latency period of MEP in the LEI group was also shorter (P=0.015). Western blotting results showed that compared with the control group, the expression levels of p-AKT/AKT and p-S6/S6 in the motor cortex of mice in the LEI group, MEI Group and HEI group were significantly increased (all P<0.05); the expression levels of IGF1 and BDNF in the motor cortex of mice in the LEI group were higher than those in the control group (both P<0.05).

Conclusion·Low intensity exercise training can activate AKT/mTOR pathway of cortical neurons and improve the nerve conduction speed, which may be related to the increased nerve growth factors.

Key words: exercise intensity, protein kinase B/ mammalian target of rapamycin signaling pathway, nerve conduction, growth factor, cortical neuron

中图分类号:

R493

易凌荣, 谭波涛, 詹祖雄, 刘媛, 殷樱, 虞乐华. 跑轮运动对小鼠皮质神经元AKT/mTOR通路活性及运动诱发电位的影响[J]. 上海交通大学学报(医学版), 2021, 41(10): 1285-1289.

Ling-rong YI, Bo-tao TAN, Zu-xiong ZHAN, Yuan LIU, Ying YIN, Le-hua YU. Effects of wheeling-running exercise on AKT/mTOR pathway activity and motor-evoked potential in cortical neurons of mice[J]. JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE), 2021, 41(10): 1285-1289.

图/表 3

图 1 4组小鼠上肢MEP分析Note：A. Motor-evoked potentials of the right upper limb of mice in each group. Dotted line—the start of stimulation. B. Quantitative analysis of N1 latency period. C. Quantitative analysis of P1 latency period. ①P=0.000, ②P=0.001, ③P=0.015, compared with the control group; ④P=0.032, compared with the HEI group.

Fig 1 Analysis of upper limb MEP in the four groups of mice

图 2 Western blotting检测4组小鼠运动皮质中AKT/mTOR通路的关键蛋白表达Note：A. Schematic drawing of motor cortex. Red—protein extraction location; Black—lateral ventricle. B/C. Expression levels (B) and quantitative analysis (C) of AKT and p-AKT. D/E. Expression levels (D) and quantitative analysis (E) of S6 and p-S6. ①P=0.009, ②P=0.046, ③P=0.024, ④P=0.000, ⑤P=0.001, compared with the control group.

Fig 2 Expression of key proteins of AKT/mTOR pathway in the motor cortex of the four groups by Western blotting

图 3 Western blotting检测对照组和LEI组小鼠运动皮质中生长因子的表达Note：A/B. Expression levels (A) and quantitative analysis (B) of IGF1. C/D. Expression levels (C) and quantitative analysis (D) of pro-BDNF and BDNF. ①P=0.000, ②P=0.013, compared with the control group.

Fig 3 Expression of growth factor in the motor cortex of mice in the control group and LEI group by Western blotting

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