运动训练对阿尔茨海默病大鼠焦虑抑郁样行为的影响。
Effects of Exercise Training on Anxious-Depressive-like Behavior in Alzheimer Rat.
机构信息
Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, Augusta, GA.
出版信息
Med Sci Sports Exerc. 2020 Jul;52(7):1456-1469. doi: 10.1249/MSS.0000000000002294.
PURPOSE
This study aimed to examine the effects of treadmill training on anxious-depressive-like behaviors of transgenic Alzheimer rats in the early stage of Alzheimer's disease (AD) and provided evidence of exercise in alleviating fear-avoidance behavior deficits.
METHODS
Male 2-month-old TgF344-AD and wild-type rats were divided into wild-type (n = 9), AD (n = 8), and AD + treadmill exercise (Exe) groups (n = 12). After 8 months of exercise, the passive avoidance test, Barnes maze task, novel object recognition test, and object location test were used to measure learning and memory function. The open-field test, elevated plus maze, sucrose preference test, and forced swim test were conducted to determine the anxious-depressive-like behavior of AD rats. Immunofluorescence staining, Western blot analysis, enzyme-linked immunosorbent assay analysis, and related assay kits were used to measure inflammatory cytokines, oxidative stress, amyloid-β production, and tau hyperphosphorylation.
RESULTS
Behavioral tests revealed that 12-month-old animals did not show any spatial learning and memory deficits but did display anxious-depressive-like behavior (open field, center time: P = 0.008; center entries: P = 0.009; line crossings: P = 0.001). However, long-term exercise significantly inhibited anxious-depressive-like behavior in AD rats (center time: P = 0.016; center entries: P = 0.004; line crossings: P = 0.033). In addition, these animals displayed increased amyloid-β deposition, tau hyperphosphorylation, microgliosis, inflammatory cytokines release, and oxidative damage, which were attenuated significantly by long-term exercise training.
CONCLUSION
Long-term exercise training alleviated anxious-depressive-like behavior and improved fear-avoidance behavior in transgenic AD rats, supporting exercise training as an effective approach to prevent anxiety, depression, and fear-avoidance behavior deficits in the early stages of AD pathogenesis.
目的
本研究旨在探讨跑步机训练对阿尔茨海默病（AD）早期转基因 AD 大鼠焦虑抑郁样行为的影响，并为运动缓解恐惧回避行为缺陷提供证据。
方法
雄性 2 月龄 TgF344-AD 和野生型大鼠分为野生型（n=9）、AD（n=8）和 AD+跑步机运动（Exe）组（n=12）。运动 8 个月后，进行被动回避测试、巴恩斯迷宫任务、新物体识别测试和物体位置测试，以测量学习和记忆功能。旷场试验、高架十字迷宫试验、蔗糖偏好试验和强迫游泳试验用于测定 AD 大鼠的焦虑抑郁样行为。免疫荧光染色、Western blot 分析、酶联免疫吸附试验分析和相关检测试剂盒用于测定炎症细胞因子、氧化应激、淀粉样β生成和 tau 过度磷酸化。
结果
行为学测试显示，12 月龄动物未出现任何空间学习记忆缺陷，但表现出焦虑抑郁样行为（旷场，中央时间：P=0.008；中央进入次数：P=0.009；穿越格线数：P=0.001）。然而，长期运动显著抑制 AD 大鼠的焦虑抑郁样行为（中央时间：P=0.016；中央进入次数：P=0.004；穿越格线数：P=0.033）。此外，这些动物表现出淀粉样β沉积增加、tau 过度磷酸化、小胶质细胞激活、炎症细胞因子释放和氧化损伤，长期运动训练显著减轻了这些变化。
结论
长期运动训练缓解了转基因 AD 大鼠的焦虑抑郁样行为，改善了其恐惧回避行为，支持运动训练作为预防 AD 发病早期焦虑、抑郁和恐惧回避行为缺陷的有效方法。
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