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
|
摘要
目的:研究表明体育锻炼可以预防睡眠不足引起的焦虑行为,然而机制尚不清楚。因此,通过探讨4周跑台运动预干预对睡眠剥夺大鼠焦虑样行为的影响,并通过检测杏仁核氧化应激水平及BDNF的表达,探讨跑台运动影响睡眠剥夺大鼠焦虑样行为的可能机制。方法:实验前将大鼠随机分为安静组(S,n=10)、运动组(E,n=10)、安静睡眠剥夺组(SSD,n=10)和睡眠剥夺运动组(ESD,n=10)。除S及SSD组大鼠外,E及ESD组大鼠进行中等强度跑台运动预干预4周,随后采用小平台水环境法建立大鼠72h睡眠剥夺模型,然后运用高架十字迷宫实验评估大鼠焦虑样行为。焦虑样行为学测试结束后,检测大鼠杏仁核超氧化物歧化酶(SOD)及过氧化氢酶(CAT)的活性,计算杏仁核BDNF的表达。结果:与安静组比较,高架迷宫实验中,72 h睡眠剥夺导致大鼠闭合臂时间百分比CT%(P<0.01)及粪便颗粒(P<0.05)增多、(OE+CE)次数(P<0.01)及开放臂时间百分比OT%(P<0.01)均显著减少,杏仁核SOD、CAT活性(P<0.01,P<0.01)及BDNF表达均显著下降(P<0.01)。而适度的跑台运动预干预可削弱睡眠剥夺引起的焦虑行为,杏仁核BDNF表达显著提升(P<0.05),抗氧化酶SOD及CAT的活性增强(P<0.05,P<0.05)。结论:规律跑台运动预干预可以通过提高睡眠剥夺大鼠杏仁核BDNF表达及抗氧化能力,对杏仁核相关功能产生保护作用,削弱睡眠剥夺大鼠的焦虑样行为。
Objetive: Evidence suggests that treadmill exercise can protect sleep deprivation induced anxiety-like behavior.However the mechanism is unclear. So we examined the impact of 4 weeks of prior regular treadmill exercise on sleep deprivation induced anxiety-like behavior and possible mechanism by detecting oxidative stress level and calculating BDNF expression of the rat amygdala. Methods: The rats were randomly divided into the follow ing subgroups: the sedentary group( S),the exercise group( E),sedentary sleep deprived group( SSD) and exercise sleep-deprived group( ESD). E and ESD rats were exposed to 4 weeks of regular treadmill exercise,and then subsequently were deprived of sleep for 72 h using small platform method. Then elevated plus-maze test( EPM) were used to evaluate the anxiety-like behavior of rats; antioxidant enzymes SOD and CAT activities in amygdala were examined and amygdala BDNF expression was calculated.Results: Compared with S group,CT% and fecal particles increased( P < 0. 01,P < 0. 05),( OE + CE) numbers( P <0. 01) and OT%( P < 0. 01) significantly decreased in EPMtest of SSD group rats; SOD and CAT activities and BDNF expression significantly reduced after 72 h sleep deprivation in SSD rats compared with the S groups. Results showed that sleep- deprived rats under moderate treadmill significantly attenuated sleep deprivation induced anxiety-like behavior,BDNF expression had a significant up-regulation( P < 0. 05) and SOD,CAT activities in amygdala significantly enhanced( P< 0. 05,P < 0. 05). Conclusion: prior regular exercise can exert a protective effect on amygdala-related functions and impairments anxiety-like behavior induced by sleep deprivation probably by inducing BDNF expression and decreasing oxidative damage in amygdala.
Objetive: Evidence suggests that treadmill exercise can protect sleep deprivation induced anxiety-like behavior.However the mechanism is unclear. So we examined the impact of 4 weeks of prior regular treadmill exercise on sleep deprivation induced anxiety-like behavior and possible mechanism by detecting oxidative stress level and calculating BDNF expression of the rat amygdala. Methods: The rats were randomly divided into the follow ing subgroups: the sedentary group( S),the exercise group( E),sedentary sleep deprived group( SSD) and exercise sleep-deprived group( ESD). E and ESD rats were exposed to 4 weeks of regular treadmill exercise,and then subsequently were deprived of sleep for 72 h using small platform method. Then elevated plus-maze test( EPM) were used to evaluate the anxiety-like behavior of rats; antioxidant enzymes SOD and CAT activities in amygdala were examined and amygdala BDNF expression was calculated.Results: Compared with S group,CT% and fecal particles increased( P < 0. 01,P < 0. 05),( OE + CE) numbers( P <0. 01) and OT%( P < 0. 01) significantly decreased in EPMtest of SSD group rats; SOD and CAT activities and BDNF expression significantly reduced after 72 h sleep deprivation in SSD rats compared with the S groups. Results showed that sleep- deprived rats under moderate treadmill significantly attenuated sleep deprivation induced anxiety-like behavior,BDNF expression had a significant up-regulation( P < 0. 05) and SOD,CAT activities in amygdala significantly enhanced( P< 0. 05,P < 0. 05). Conclusion: prior regular exercise can exert a protective effect on amygdala-related functions and impairments anxiety-like behavior induced by sleep deprivation probably by inducing BDNF expression and decreasing oxidative damage in amygdala.
引文
[1]Wei Zhao,Jun Wang,Weina Bi,et al.Novel application of braintargeting polyphenol compounds in sleep deprivation-induced cognitive dysfunction[J].Neurochemistry International,2015,89:191-197.
[2]Centers for Disease Control and Prevention(CDC).Effect of short sleep duration on daily activities-United States,2005-2008[J].MMWR Morb Mortal Wkly Rep,2011,60(8):239-242.
[3]Mc Coy JG,Strecker RE.The cognitive cost of sleep lost[J].Neurobiology of Learning and Memory,2011,96:564-582.
[4]MR.Zielinski,JM Davis,JR Fadel,et al.Influence of chronic moderate sleep restriction and exercise training on anxiety,spatial memory,and associated neurobiological measures in mice[J].Behavioural Brain Research,2013,250:74-80.
[5]Takuya Kanamaru,Naomi Kamimura,Takashi Yokota,et al.Oxidative stress accelerates amyloid deposition and memory impairment in a double-transgenic mouse model of Alzheimer’s disease[J].Neuroscience Letters,2015,587:126-131.
[6]Kumar A,Singh A,Kumar P.Possible involvement of GABAergic mechanism in protective effect of melatonin against sleep deprivation-induced behavior modi?cation and oxidative damage in mice[J].Indian J Exp Biol,2011,49(3):211-218.
[7]M Davis,DL Walker,L Miles,et al.Phasic vs sustained fear in rats and humans:role of the extended amygdala in fear vs anxiety[J].Neuropsychopharmacology,2010,35:105-135.
[8]Zielinski MR,Davis JM,Fadel JR,et al.Influence of chronic moderate sleep restriction and exercise training on anxiety,spatial memory,and associated neurobiological measures in mice[J].Behav Brain Res,2013,250:74-80.
[9]Lalanza JF,Sanchez-Roige S,Gagliano H,et al.Physiological and behavioural consequences of long-term moderate treadmill exercise[J].Psychoneuroendocrinology,2012,37:1745-1754.
[10]Vollert C,Zagaar M,Hovatta I,et al.Exercise prevents sleep deprivation-associated anxiety-like behavior in rats:potential role of oxidative stress mechanisms[J].Behavioural Brain Research,2011,224:233-240.
[11]Saadati H,Sheibani V,Esmaeili-Mahani S,et al.Prior regular exercise reverses the decreased effects of sleep deprivation on brain-derived neurotrophic factor levels in the hippocampus of ovariectomized female rats[J].Regulatory Peptides,2014(194-195):11-15.
[12]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].Neurobiol Dis,2012,45(3):1153-1162.
[13]Suchecki D,Tiba PA,Tuk S.Hormonal and behavioral responses of paradoxical sleep-deprived rats to the elevated plus maze[J].J Neuroendocrinol,2002,14:549-554.
[14]P Sagaspe,M Sanchez-Ortuno,A Charles,et al.Effects of sleep deprivation on Color-Word,Emotional,and Specific Stroop interference and on self-reported anxiety[J].Brain Cogn,2005,60:76-87.
[15]PL Franzen,GJ Siegle,DJ Buysse.Relationships between affect,vigilance,and sleepiness following sleep deprivation[J].Journal of Sleep Research,2008,17:34-41.
[16]ET Kahn-Greene,DB Killgore,GH Kamimori,et al.The effects of sleep deprivation on symptoms of psychopathology in healthy adults[J].Sleep Medicine,2007,8:215-221.
[17]PY Yang,KH Ho,HC Chen,et al.Exercise training improves sleep quality in middle-aged and older adults with sleep problems:a systematic review[J].Journal of Physiotherapy,2012,58(3):157-163.
[18]SD Youngstedt,CE Kline.Epidemiology of exercise and sleep[J].Sleep and Biological Rhythms,2006(3):215-221.
[19]Fulk LJ,Stock HS,Marshall JD,et al.Chronic treadmill training reduces acute anxiety-related behaviors in rats[J].Int J Sports Med,2003,24:1-5.
[20]JK Kiecolt-Glaser,ES Epel,MA Belury,et al.Omega-3 fatty acids,oxidative stress,and leukocyte telomere length:a randomized controlled trial[J].Brain,Behavior,and Immunity,2013,28:16-24.
[21]Singh R,Kiloung J,Singh S,et al.Effect of paradoxical sleep deprivation on oxidative stress parameters in brain regions of adult and old rats[J].Biogerontology,2008,9(3):153-162.
[22]S Salim,N Sarraj,M Taneja,et al.Moderate treadmill exercise prevents oxidative stress-induced anxiety-like behavior in rats[J].Behav Brain Res,2010,208:545-552.
[23]F Cechetti,PV Woem,VR Elsner,et al.Forced treadmill exercise prevents oxidative stress and memory deficits following chronic cerebral hypoperfusion in the rat[J].Neurobiology of Learning and Memory,2012,97:90-96.
[24]AH Nagahara,DA Merrill.Neuroprotective effects of brain-derived neurotrophic factor in rodent and primate models of Alzheimer’s disease[J].Nature Medicine,2009,15(3):331-337.
[25]H Sei,D Saitoh,K Yamamoto,et al.Differential effect of short-term REM sleep deprivation on NGF and BDNF protein levels in the rat brain[J].Brain Research,2000,877:387-390.
[26]R Guzman-Marin,Z Ying,N Suntsova,et al.Suppression of hippocampal plasticity-related gene expression by sleep deprivation in rats[J].Journal of Physiology,2006,575:807-819.
[27]KS Lee,TA Alvarenga,C Guindalini,et al.Validation of commonly used reference genes for sleep-related gene expression studies[J].BMC Mol Biol,2009,10:45-53.
[28]IA Alhaider,AM Aleisa,TT Tran,et al.Caffeine prevents sleep lossinduced deficits in long-term potentiation and related signaling molecules in the dentate gyrus[J].European Journal of Neuroscience,2010,31:1368-1376.
[29]CW Cotman,NC Berchtold,LA Christie.Exercise builds brain health:key roles of growth factor cascades and inflammation[J].Trends Neurosci,2007,30:464-472.
[30]F Kapczinski,BN Frey,AC Andreazza,et al.Increased oxidative stress as a mechanism for decreased BDNF levels in acute manic episodes[J].Rev Bras Psiquiatr,2008,30(3):243-245.
[31]A Wu,Z Ying,F Gomez-Pinilla.The interplay between oxidative stress and brain-derived neurotrophic factor modulates the outcome of a saturated fat diet on synaptic plasticity and cognition[J].Eur J Neurosci,2004,19(7):1699-1707.
[2]Centers for Disease Control and Prevention(CDC).Effect of short sleep duration on daily activities-United States,2005-2008[J].MMWR Morb Mortal Wkly Rep,2011,60(8):239-242.
[3]Mc Coy JG,Strecker RE.The cognitive cost of sleep lost[J].Neurobiology of Learning and Memory,2011,96:564-582.
[4]MR.Zielinski,JM Davis,JR Fadel,et al.Influence of chronic moderate sleep restriction and exercise training on anxiety,spatial memory,and associated neurobiological measures in mice[J].Behavioural Brain Research,2013,250:74-80.
[5]Takuya Kanamaru,Naomi Kamimura,Takashi Yokota,et al.Oxidative stress accelerates amyloid deposition and memory impairment in a double-transgenic mouse model of Alzheimer’s disease[J].Neuroscience Letters,2015,587:126-131.
[6]Kumar A,Singh A,Kumar P.Possible involvement of GABAergic mechanism in protective effect of melatonin against sleep deprivation-induced behavior modi?cation and oxidative damage in mice[J].Indian J Exp Biol,2011,49(3):211-218.
[7]M Davis,DL Walker,L Miles,et al.Phasic vs sustained fear in rats and humans:role of the extended amygdala in fear vs anxiety[J].Neuropsychopharmacology,2010,35:105-135.
[8]Zielinski MR,Davis JM,Fadel JR,et al.Influence of chronic moderate sleep restriction and exercise training on anxiety,spatial memory,and associated neurobiological measures in mice[J].Behav Brain Res,2013,250:74-80.
[9]Lalanza JF,Sanchez-Roige S,Gagliano H,et al.Physiological and behavioural consequences of long-term moderate treadmill exercise[J].Psychoneuroendocrinology,2012,37:1745-1754.
[10]Vollert C,Zagaar M,Hovatta I,et al.Exercise prevents sleep deprivation-associated anxiety-like behavior in rats:potential role of oxidative stress mechanisms[J].Behavioural Brain Research,2011,224:233-240.
[11]Saadati H,Sheibani V,Esmaeili-Mahani S,et al.Prior regular exercise reverses the decreased effects of sleep deprivation on brain-derived neurotrophic factor levels in the hippocampus of ovariectomized female rats[J].Regulatory Peptides,2014(194-195):11-15.
[12]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].Neurobiol Dis,2012,45(3):1153-1162.
[13]Suchecki D,Tiba PA,Tuk S.Hormonal and behavioral responses of paradoxical sleep-deprived rats to the elevated plus maze[J].J Neuroendocrinol,2002,14:549-554.
[14]P Sagaspe,M Sanchez-Ortuno,A Charles,et al.Effects of sleep deprivation on Color-Word,Emotional,and Specific Stroop interference and on self-reported anxiety[J].Brain Cogn,2005,60:76-87.
[15]PL Franzen,GJ Siegle,DJ Buysse.Relationships between affect,vigilance,and sleepiness following sleep deprivation[J].Journal of Sleep Research,2008,17:34-41.
[16]ET Kahn-Greene,DB Killgore,GH Kamimori,et al.The effects of sleep deprivation on symptoms of psychopathology in healthy adults[J].Sleep Medicine,2007,8:215-221.
[17]PY Yang,KH Ho,HC Chen,et al.Exercise training improves sleep quality in middle-aged and older adults with sleep problems:a systematic review[J].Journal of Physiotherapy,2012,58(3):157-163.
[18]SD Youngstedt,CE Kline.Epidemiology of exercise and sleep[J].Sleep and Biological Rhythms,2006(3):215-221.
[19]Fulk LJ,Stock HS,Marshall JD,et al.Chronic treadmill training reduces acute anxiety-related behaviors in rats[J].Int J Sports Med,2003,24:1-5.
[20]JK Kiecolt-Glaser,ES Epel,MA Belury,et al.Omega-3 fatty acids,oxidative stress,and leukocyte telomere length:a randomized controlled trial[J].Brain,Behavior,and Immunity,2013,28:16-24.
[21]Singh R,Kiloung J,Singh S,et al.Effect of paradoxical sleep deprivation on oxidative stress parameters in brain regions of adult and old rats[J].Biogerontology,2008,9(3):153-162.
[22]S Salim,N Sarraj,M Taneja,et al.Moderate treadmill exercise prevents oxidative stress-induced anxiety-like behavior in rats[J].Behav Brain Res,2010,208:545-552.
[23]F Cechetti,PV Woem,VR Elsner,et al.Forced treadmill exercise prevents oxidative stress and memory deficits following chronic cerebral hypoperfusion in the rat[J].Neurobiology of Learning and Memory,2012,97:90-96.
[24]AH Nagahara,DA Merrill.Neuroprotective effects of brain-derived neurotrophic factor in rodent and primate models of Alzheimer’s disease[J].Nature Medicine,2009,15(3):331-337.
[25]H Sei,D Saitoh,K Yamamoto,et al.Differential effect of short-term REM sleep deprivation on NGF and BDNF protein levels in the rat brain[J].Brain Research,2000,877:387-390.
[26]R Guzman-Marin,Z Ying,N Suntsova,et al.Suppression of hippocampal plasticity-related gene expression by sleep deprivation in rats[J].Journal of Physiology,2006,575:807-819.
[27]KS Lee,TA Alvarenga,C Guindalini,et al.Validation of commonly used reference genes for sleep-related gene expression studies[J].BMC Mol Biol,2009,10:45-53.
[28]IA Alhaider,AM Aleisa,TT Tran,et al.Caffeine prevents sleep lossinduced deficits in long-term potentiation and related signaling molecules in the dentate gyrus[J].European Journal of Neuroscience,2010,31:1368-1376.
[29]CW Cotman,NC Berchtold,LA Christie.Exercise builds brain health:key roles of growth factor cascades and inflammation[J].Trends Neurosci,2007,30:464-472.
[30]F Kapczinski,BN Frey,AC Andreazza,et al.Increased oxidative stress as a mechanism for decreased BDNF levels in acute manic episodes[J].Rev Bras Psiquiatr,2008,30(3):243-245.
[31]A Wu,Z Ying,F Gomez-Pinilla.The interplay between oxidative stress and brain-derived neurotrophic factor modulates the outcome of a saturated fat diet on synaptic plasticity and cognition[J].Eur J Neurosci,2004,19(7):1699-1707.