跑台运动对慢性睡眠剥夺大鼠行为学改变、海马炎症因子及海马齿状回BDNF/Trk B信号通路的影响
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摘要
目的:研究认为,体育运动可以改善慢性睡眠缺失引起的认知功能下降和情绪障碍,海马DG区在学习、记忆和空间编码中起着关键作用,并且对睡眠缺失高度敏感。因此本研究主要通过测量8周跑台运动对慢性睡眠剥夺(chronic sleep deprivation,CSD)大鼠海马炎症因子(IL-6及TNF-a)水平和海马DG区BDNF及TrkB表达的影响,探讨跑台运动改善CSD大鼠认知功能及焦虑样行为的可能机制。方法:将44只大鼠随机分为对照组(SG)、运动组(EX)、慢性睡眠剥夺组(CSD)和睡眠剥夺运动组(CSD+E)。随后,CSD和CSD+E组大鼠采用多平台水环境法制作CSD模型,同时,EX和CSD+E组大鼠进行8周中等强度跑台运动(1h/day/6d/week)。跑台运动及CSD结束后,采用高架迷宫实验(EPM)评估大鼠焦虑样行为,八臂迷宫实验(ERM)评估大鼠空间学习记忆能力;除外,海马炎症因子(IL-6、TNF-a)水平及海马DG区BDNF及其受体TrkB表达被测量。结果:1)与SG组比较,ERM实验中,CSD组大鼠错误潜伏期缩短,训练达到标准次数及TM显著增多(P均<0.01)、CN减少(P<0.05);EPM实验中,CSD组大鼠ORT、ORE均显著减少,焦虑指数显著增加(P均<0.01);海马促炎因子IL-6及TNF-a水平显著增加(P均<0.01);海马DG区BDNF及TrkB表达显著降低(P均<0.01);2)8周跑台运动显著削弱了大鼠焦虑样行为,阻止了大鼠空间学习记忆能力的下降,海马促炎因子IL-6及TNF-a水平明显下降(P<0.05,P<0.01),海马DG区BDNF及TrkB表达均显著增强(P<0.05,P<0.01)。结论:中等强度跑台运动可以增强CSD大鼠学习记忆能力,削弱大鼠焦虑样行为,可能与此运动减弱海马炎症反应、增加海马DG区BDNF及其受体TrkB表达,从而增强BDNF/Trk B信号通路对CSD大鼠海马的神经保护作用有关。
Objective: Physical exercise is known to improve the cognitive function decline and emotional disorders induced by chronic sleep deprivation(CSD). Therefore, the aim of this study was to examine the effects of 8 weeks treadmill exercise on CSD induced spatial memory and anxiety-like behavior by measuring hippocampus inflammatory biomarkers levels(IL-6 and TNF-α) and hippocampus DG(dentate gyrus) BDNF and TrkB expression levels. Methods: 44 rats were randomly allocated into either a sedentary control group(SG), an exercise group(EX), a chronic sleep deprived group(CSD), or a CSD+exercise group(CSD+E). The sleep deprivation was induced by using modified multiple platform method(18 h/day, for 8 weeks) in CSD and CSD+E groups. Simultaneously, the rats in EX and CSD+E groups were conducted treadmill exercise training for 8 weeks(1 h/day, 6 d/week). Thereafter, the anxiety-related behavior was assessed with the elevated-plus maze(EPM), and the spatial learning and memory were assessed by using the eight arm maze test(ERM). Additionally, the hippocampus inflammatory biomarkers(IL-6 and TNF-α) and hippocampus DG BDNF and TrkB expression levels were measured. Results: 1) Compared to the sedentary control rats, the latency of memory error was shorted in CSD rats, the numbers of achieving training standard and total memory errors were significantly increased(P<0.01, respectively); in addition, the correct numbers before the first error was decreased(P<0.05) in the ERM test. In the EPM test, the time and entries of open arm was significantly decreased in CSD rats by comparing with SG group, and the anxiety index was increased(P<0.01, respectively); the TNF-α and IL-6 concentrations in hippocampus were increased(P<0.01), and the expression levels of BNDF and TrkB in hippocampus DG were decreased(P<0.01). 2) 8 week treadmill exercise training was significantly attenuated anxiety-related behavior and prevented spatial learning and memory impairment; the levels of IL-6 and TNF-α in hippocampus were decreased; moreover, the expression levels of BDNF and TrkB in hippocampus DG were significantly increased after exercise training. Conclusions: Moderate-intensity treadmill exercise improved the learning and memory ability and attenuate anxiety like behavior in the CSD rats. The possible mechanisms might be related to the exercise preventing proinflammatory responses in hippocampus, and increasing BDNF and TrkB expression in hippocampus DG and improving the nerve protective effect via BDNF/TrkB pathway.
Objective: Physical exercise is known to improve the cognitive function decline and emotional disorders induced by chronic sleep deprivation(CSD). Therefore, the aim of this study was to examine the effects of 8 weeks treadmill exercise on CSD induced spatial memory and anxiety-like behavior by measuring hippocampus inflammatory biomarkers levels(IL-6 and TNF-α) and hippocampus DG(dentate gyrus) BDNF and TrkB expression levels. Methods: 44 rats were randomly allocated into either a sedentary control group(SG), an exercise group(EX), a chronic sleep deprived group(CSD), or a CSD+exercise group(CSD+E). The sleep deprivation was induced by using modified multiple platform method(18 h/day, for 8 weeks) in CSD and CSD+E groups. Simultaneously, the rats in EX and CSD+E groups were conducted treadmill exercise training for 8 weeks(1 h/day, 6 d/week). Thereafter, the anxiety-related behavior was assessed with the elevated-plus maze(EPM), and the spatial learning and memory were assessed by using the eight arm maze test(ERM). Additionally, the hippocampus inflammatory biomarkers(IL-6 and TNF-α) and hippocampus DG BDNF and TrkB expression levels were measured. Results: 1) Compared to the sedentary control rats, the latency of memory error was shorted in CSD rats, the numbers of achieving training standard and total memory errors were significantly increased(P<0.01, respectively); in addition, the correct numbers before the first error was decreased(P<0.05) in the ERM test. In the EPM test, the time and entries of open arm was significantly decreased in CSD rats by comparing with SG group, and the anxiety index was increased(P<0.01, respectively); the TNF-α and IL-6 concentrations in hippocampus were increased(P<0.01), and the expression levels of BNDF and TrkB in hippocampus DG were decreased(P<0.01). 2) 8 week treadmill exercise training was significantly attenuated anxiety-related behavior and prevented spatial learning and memory impairment; the levels of IL-6 and TNF-α in hippocampus were decreased; moreover, the expression levels of BDNF and TrkB in hippocampus DG were significantly increased after exercise training. Conclusions: Moderate-intensity treadmill exercise improved the learning and memory ability and attenuate anxiety like behavior in the CSD rats. The possible mechanisms might be related to the exercise preventing proinflammatory responses in hippocampus, and increasing BDNF and TrkB expression in hippocampus DG and improving the nerve protective effect via BDNF/TrkB pathway.
引文
崔建梅,郭燕兰,赵行瑞,等.2016.运动预干预通过增强杏仁核抗氧化能力及BDNF表达改善睡眠剥夺大鼠焦虑行为[J].沈阳体育学院学报,35(3):79-84.
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LALANZA J F,SANCHEZ-ROIGE S,GAGLIANO H,et al.,2012.Physiological and behavioural consequences of long-term moderate treadmill exercise[J].Psychoneuroendocrinology,7(11):1745-54.
LEKANDER M,ANDREASSON A N,KECKLUND G,et al.,2013.Subjective health perception in healthy young men changes in response to experimentally restricted sleep and subsequent recovery sleep[J].Brain Behav Immun,34(11):43-46.
LIU X,CHAN C B,JANG S W,et al.,2010.A synthetic7,8-dihydroxyflavone derivative promotes neurogenesis and exhibits potent antidepressant effect[J].J Med Chem,53(23):8274-86.
MANCHANDA S,SINGH H,KAUR T,et al.,2018.Low-grade neuroinflammation due to chronic sleep deprivation results in anxiety and learning and memory impairments[J].Mol Cell Biochem,449(1-2):63-72.
MARKS CA,WAYNER M J,2005.Effects of sleep disruption on rat dentate granule cell LTP in vivo[J].Brain Res Bull,66(2):114-119.
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