有氧运动对慢性应激大鼠空间学习记忆及海马齿状回BDNF表达的影响
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摘要
通过研究跑台运动对慢性应激大鼠空间学习记忆能力及海马齿状回脑源性神经营养因子(BDNF)含量的改变,探讨有氧运动改善慢性应激大鼠认知能力的可能机制。方法:将健康成年Sprague-Dawley(8周)大鼠随机分为3组:正常对照组(C,n=10)、应激模型组(CUS,n=10)及应激运动组(CUS+E,n=10)3组,通过慢性不可预知应激建立大鼠抑郁模型。CUS+E组大鼠采取4周跑台运动,通过八臂迷宫实验观察跑台运动对应激大鼠学习记忆能力的影响;八臂迷宫实验结束后用ABC免疫组织染色法检测各组大鼠海马齿状回BDNF的分布。结果:与CUS组大鼠比较,CUS+E组大鼠八臂迷宫实验中大鼠完成八臂迷宫探索时间(P<0.05)及进入放饵料臂平均潜伏期均显著缩短(P<0.05),参考记忆(P<0.05)及总记忆错误次数(P<0.05)均显著增多;海马DG区BDNF数量(P<0.05)及面积(P<0.05)均显著增多。结论:当前研究发现4周跑台运动可能通过激活海马DG区BDNF通路,增强海马DG区BDNF的表达,改善慢性应激大鼠的学习记忆能力。
Objective:To observe the effects of treadmill exercise on the learning,memory and Hippocampal DG(dentate gyrus) BDNF(brain derived neurotrophic factor) expression in CUS(chronic unpredictable mild stress)rats and explore the possible mechanism of regular aerobic exercise to improve learning and memory.Methods:30 adult SD(Sprague-Dawley) male rats were randomly assigned into 3 groups:control group(C),chronic unpredictable stress group rats(CUS) and stress exercise group(CUS+E).All rats were subjected to CUS except the control group.The learning and memory ability of rats were tested by radial arm maze test(CUS) after CUS+E group rats received 4-week treadmill exercise.Subsequently,ABC immunohistochemical staining detected BDNF expression in Hippocampus DG in every group rats.Results:Compared with the CUS group rats,the time of completing 8-arms radial maze and latency of entering into bait arms in ERM test significantly shortened(P<0.05,P<0.05),reference memory errors and total memory errors in RAM test significantly decreased(P<0.05,P<0.05); number and area of BDNF significantly increased in Hippocampal DG(P<0.05,P<0.05) in CUE+E group rats.Conclusion:The present experiment verified that 4-week treadmill exercise reverses stress-induced learning and memory impaired via an increase in BDNF signaling and may increase BDNF expression in Hippocampal DG.
Objective:To observe the effects of treadmill exercise on the learning,memory and Hippocampal DG(dentate gyrus) BDNF(brain derived neurotrophic factor) expression in CUS(chronic unpredictable mild stress)rats and explore the possible mechanism of regular aerobic exercise to improve learning and memory.Methods:30 adult SD(Sprague-Dawley) male rats were randomly assigned into 3 groups:control group(C),chronic unpredictable stress group rats(CUS) and stress exercise group(CUS+E).All rats were subjected to CUS except the control group.The learning and memory ability of rats were tested by radial arm maze test(CUS) after CUS+E group rats received 4-week treadmill exercise.Subsequently,ABC immunohistochemical staining detected BDNF expression in Hippocampus DG in every group rats.Results:Compared with the CUS group rats,the time of completing 8-arms radial maze and latency of entering into bait arms in ERM test significantly shortened(P<0.05,P<0.05),reference memory errors and total memory errors in RAM test significantly decreased(P<0.05,P<0.05); number and area of BDNF significantly increased in Hippocampal DG(P<0.05,P<0.05) in CUE+E group rats.Conclusion:The present experiment verified that 4-week treadmill exercise reverses stress-induced learning and memory impaired via an increase in BDNF signaling and may increase BDNF expression in Hippocampal DG.
引文
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[24]MOKHTARIZAER A,GHODRATI-JALDBAKHAN S,VAFAEI A A,et al.Effects of voluntary and treadmill exercise on spontaneous withdrawal signs,cognitive deficits and alterations in apoptosis-associated proteins in morphine-dependent rats[J].Behav Brain Res,2014(271):160.
[25]KEMPERMANN G,KRONENBERG G.Depressed new neurons-adult hippocampal neurogenesis and a cellular plasticity hypothesis of major depression[J].Biol Psychiatry,2003,54(5):499.
[26]TRAVIS S,COUPLAND N J,SILVERSONE P H,et al.Dentate gyrus volume and memory performance in major depressive disorder[J].J Affect Disord,2015(172):159.
[27]ZHANG L,BENEDEK D M,FULLERTON C S,et al.PTSD risk is associated with BDNF Val66Met and BDNF overexpression[J].Molecular Psychiatry,2014,19(1):8.
[28]LEE B H,KIM Y K.The Roles of BDNF in the Pathophysiology of Major Depression and in Antidepressant Treatment[J].Psychiatry Investigation,2010,7(4):231.
[29]DEXIANG L,KAI X,XUDONG Y,et al.Resveratrol reverses the effects of chronic unpredictable mild stress on behavior,serum corticosterone levels and BDNF expression in rats[J].Behavioural Brain Research,2014,264(5):9.
[30]KIM D M,LEEM Y H.Chronic stress-induced memory deficits are reversed by regular exercise via AMPK-mediated BDNF induction[J].Neuroscience,2016,324(2):271.
[31]PESIC V,STANIC D,PETROVIC J,et al.Oxytocin affects changes in behaviour,BDNF and Ki-67 expression in hippocampus,caused by chronic corticosterone treatment[J].European Neuropsychopharmacology,2016,26(2):289.
[32]HAN H,WU L M,HAN M X,et al.Diabetes impairs spatial learning and memory and hippocampal neurogenesis via BDNF in rats with transient global ischemia[J].Brain Research Bulletin,2016(124):269.
[33]ALOMARI M A,KHABOUR O F,ALZOUBI K H,et al.Forced and voluntary exercises equally improve spatial learning and memory and hippocampal BDNF levels[J].Behavioural Brain Research,2013,247(7):34.
[34]FANG Z H,LEE C H,SEO M K,et al.Effect of treadmill exercise on the BDNF-mediated pathway in the hippocampus of stressed rats[J].Neu roscience Research,2013,76(4):187.
[35]KWON D H,KIM B S,CHANG H,et al.Exercise ameliorates cognition impairment due to restraint stress-induced oxidative insult and reduced BDNF level[J].Biochemical&Biophysical Research Communications,2013,434(2):245.
[36]ZHANG Y,LAN R,WANG J,et al.Acupuncture reduced apoptosis and up-regulated BDNF and GDNF expression in hippocampus following hypoxia-ischemia in neonatal rats[J].Journal of Ethnopharmacology,2015(172):124.
[2]COOPER A A,STRUNK D R,RYAN E T,et al.The therapeutic alliance and therapist adherence as predictors of dropout from cognitive therapy for depression when combined with antidepressant medicatio n[J].Journal of Behavior Therapy&Experimental Psychiatry,2016(50):113.
[3]LI Y C,SHEN J D,LI J,et al.Chronic treatment with baicalin prevents the chronic mild stress-induced depressive-like behavior:involving the inhibition of cyclooxygenase-2 in rat brain[J].Progress in neuro-psychopharmacology&biological psychiatry,2013,40(2):138.
[4]GE L,ZHU M M,YANG J Y,et al.Differential proteomic analysis of the anti-depressive effects of oleamide in a rat chronic mild stress model of depression[J].Pharmacology Biochemistry&Behavior,2015(131):77.
[5]LIU D,ZHEN W,GAO Z,et al.Effects of curcumin on learning and memory deficits,BDNF,and ERK protein expression in rats exposed to chronic unpredictable stress[J].Behavioural Brain Research,2014(271):116.
[6]RADAHMADI M,HOSSEINI N,NASIMI A.Effect of chronic stress on short and long-term plasticity in dentate gyrus;Study of recovery and adaptation[J].Neuroscience,2014(280):121.
[7]KESNER R P,KIRK R A,YU Z,et al.Dentate gyrus supports slope recognition memory,shades of grey-context pattern separation and recognition memory,and CA3 supports pattern completion for object memory[J].Neurobiology of Learning&Memory,2016(129):29.
[8]MUNNO D,STERPONE S,FANIA S,et al.Plasma brain derived neurotrophic factor levels and neuropsychological aspects of depressed patients treated with paroxetine[J].Panminerva Medica,2013,55(4):377.
[9]LEEM Y H,YOON S S,KIM Y H,et al.Disrupted MEK/ERK signaling in the medial orbital cortex and dorsal endopiriform nuclei of the prefrontal cortex in a chronic restraint stress mouse model of depression[J].Neuroscience Letters,2014,580(10):163.
[10]DESCHAMPS T,THOMASOLLIVIER V,SAUVAGET A,et al.Balance characteristics in patients with major depression after a two-month walking exercise program:A pilot study[J].Gait&Posture,2015,42(4):590.
[11]JR A A,CASTRO A A,MOREIRA E L,et al.Short bouts of mild-intensity physical exercise improve spatial learning and memory in aging rats:involvement of hippocampal plasticity via AKT,CREB and BDNF signaling[J].Mechanisms of Ageing&Development,2011,132(11/12):560.
[12]BRAUN A A,SKELTON M R,VORHEES C V,et al.Comparison of the elevated plus and elevated zero mazes in treated and untreated male Sprague Dawley rats:Effects of anxiolytic and anxiogenic agents[J].Pharmacology Biochemistry&Behavior,2011,97(3):406.
[13]ZAGAAR M,ALHAIDER I,DAO A,et al.The beneficial effects of regular exercise on cognition in REM sleep deprivation:behavioral,electrophysiological and molecular evidence[J].Neurobiology of Disease,2012,45(3):1153.
[14]SPIEKER E A,ASTUR R S,WEST J T,et al.Spatial memory deficits in a virtual reality eight-arm radial maze in schizophrenia[J].Schizophrenia Research,2012,135(1/3):84.
[15]WU R,SHUI L,WANG S,et al.Bilobalide alleviates depression-like behavior and cognitive deficit induced by chronic unpredictable mild stress in mice[J].Behavioural Pharmacology,2016,27(7):596.
[16]UYSAL N,SISMAN A R,DAYI A,et al.Acute footshock-stress increases spatial learning-memory and correlates to increased hippocampal BDNF and VEGF and cell numbers in adolescent male and female rats[J].Neurosci Lett,2012,514(2):141.
[17]PESARICO A P,SARTORI G,BRüNING C A,et al.A novel isoquinoline compound abolishes chronic unpredictable mild stress-induced depressive-like behavior in mice[J].Behavioural Brain Research,2016(307):73.
[18]SHEN H,TONG L,BALAZS R,et al.Physical activity elicits sustained activation of the cyclic AMP response element-binding protein and mi togen-activated protein kinase in the rat hippocampus[J].Neuro science,2001,107(2):219.
[19]STANTON R,REABURN P.Exercise and the treatment of depression:A review of the exercise program variables[J].Journal of Science&Medicine in Sport,2014,17(2):177.
[20]DIMEO F,BAUER M,VARAHRAM I,et al.Benefits from aerobic exercise in patients with major depression:a pilot study[J].British Journal of Sports Medicine,2001,35(2):114.
[21]CETINKAYA C,SISMAN A R,KIRAY M,et al.Positive effects of aerobic exercise on learning and memory functioning,which correlate with hippocampal IGF-1 increase in adolescent rat s[J].Neuroscience Let ters,2013,549(33):177.
[22]RADAHMADI M,ALAEI H,SHARIFI M R,et al.Preventive and therapeutic effect of treadmill running on chronic stress-induced memory deficit in rats[J].Journal of Bodywork&Movement Therapies,2015,19(2):238.
[23]RADAK Z,TOLDY A,SZABO Z,et al.The effects of training and detraining on memory,neurotrophins and oxidative stress markers in rat brain[J].Neurochemistry International,2006,49(4):387.
[24]MOKHTARIZAER A,GHODRATI-JALDBAKHAN S,VAFAEI A A,et al.Effects of voluntary and treadmill exercise on spontaneous withdrawal signs,cognitive deficits and alterations in apoptosis-associated proteins in morphine-dependent rats[J].Behav Brain Res,2014(271):160.
[25]KEMPERMANN G,KRONENBERG G.Depressed new neurons-adult hippocampal neurogenesis and a cellular plasticity hypothesis of major depression[J].Biol Psychiatry,2003,54(5):499.
[26]TRAVIS S,COUPLAND N J,SILVERSONE P H,et al.Dentate gyrus volume and memory performance in major depressive disorder[J].J Affect Disord,2015(172):159.
[27]ZHANG L,BENEDEK D M,FULLERTON C S,et al.PTSD risk is associated with BDNF Val66Met and BDNF overexpression[J].Molecular Psychiatry,2014,19(1):8.
[28]LEE B H,KIM Y K.The Roles of BDNF in the Pathophysiology of Major Depression and in Antidepressant Treatment[J].Psychiatry Investigation,2010,7(4):231.
[29]DEXIANG L,KAI X,XUDONG Y,et al.Resveratrol reverses the effects of chronic unpredictable mild stress on behavior,serum corticosterone levels and BDNF expression in rats[J].Behavioural Brain Research,2014,264(5):9.
[30]KIM D M,LEEM Y H.Chronic stress-induced memory deficits are reversed by regular exercise via AMPK-mediated BDNF induction[J].Neuroscience,2016,324(2):271.
[31]PESIC V,STANIC D,PETROVIC J,et al.Oxytocin affects changes in behaviour,BDNF and Ki-67 expression in hippocampus,caused by chronic corticosterone treatment[J].European Neuropsychopharmacology,2016,26(2):289.
[32]HAN H,WU L M,HAN M X,et al.Diabetes impairs spatial learning and memory and hippocampal neurogenesis via BDNF in rats with transient global ischemia[J].Brain Research Bulletin,2016(124):269.
[33]ALOMARI M A,KHABOUR O F,ALZOUBI K H,et al.Forced and voluntary exercises equally improve spatial learning and memory and hippocampal BDNF levels[J].Behavioural Brain Research,2013,247(7):34.
[34]FANG Z H,LEE C H,SEO M K,et al.Effect of treadmill exercise on the BDNF-mediated pathway in the hippocampus of stressed rats[J].Neu roscience Research,2013,76(4):187.
[35]KWON D H,KIM B S,CHANG H,et al.Exercise ameliorates cognition impairment due to restraint stress-induced oxidative insult and reduced BDNF level[J].Biochemical&Biophysical Research Communications,2013,434(2):245.
[36]ZHANG Y,LAN R,WANG J,et al.Acupuncture reduced apoptosis and up-regulated BDNF and GDNF expression in hippocampus following hypoxia-ischemia in neonatal rats[J].Journal of Ethnopharmacology,2015(172):124.