有氧运动改善老年脑小血管病大鼠淡漠行为机制的研究
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摘要
目的观察有氧运动对老年脑小血管病(CSVD)大鼠长期慢性脑缺血后出现的淡漠行为的改善作用,并探讨其可能的神经保护机制。方法 48只老年雄性SD大鼠采用完全随机化方法分为正常对照组(不作任何处理)、假手术组(假手术后4周进行游泳锻炼)、脑缺血组[接受双侧颈动脉结扎(BCCAO)处理]和游泳组(BCCAO术后4周进行游泳锻炼) 4组。术前对全部正常大鼠进行挖穴和社交试验的测定,术后8周再次进行测定,并对大鼠的淡漠行为进行评估;通过固蓝染色观察大鼠基底节区白质髓鞘脱失情况;利用免疫荧光法测定大鼠基底节区离子钙接头蛋白分子(Iba-1)、胶质纤维酸性蛋白(GFAP)的表达;利用western blot法测定大鼠基底节区髓鞘碱性蛋白(MBP)、白细胞介素1(IL-1)、IL-6及肿瘤坏死因子(TNF-α)的表达。结果与正常对照组和假手术组比较,脑缺血组大鼠挖穴和社交能力明显下降(P<0. 05),基底节区出现明显的髓鞘脱失,Iba-1、GFAP阳性星形胶质细胞数目均增高(P<0. 05),MBP蛋白水平明显降低(P<0. 05),IL-1、IL-6、TNF-α水平明显增高(P<0. 05)。游泳组较脑缺血组挖穴能力明显上升(P<0. 05),Iba-1、GFAP阳性星形胶质细胞数目降低(P<0. 05),MBP水平升高(P<0. 05),IL-1、IL-6水平降低(P<0. 05),TNF-α水平无明显变化。结论有氧运动可能是通过减少CSVD大鼠基底节区小胶质细胞活化释放炎症因子,增加髓鞘再生从而改善大鼠慢性脑缺血导致的淡漠行为。
Objective To observe the effects of aerobic exercise on the indifferent behavior induced by long-term chronic cerebral ischemia in the elderly rats with cerebral small-vessel disease( CSVD),and to invetstigate the possible neuroprotective mechanism. Methods Forty-eight adult male Sprague-Dawley rats were randomly divided into normal control group, sham-operated group( swimming training for 4 weeks without surgery),cereral ischemia group [receiving bilateral carotid artery ligation( BCCAO) only] and swimming group( receiving BCCAO and swimming training for 4 weeks). Before and 8 weeks after the operation,all the rats received digging and social tests,and the indifference behaviors of the rats were evaluated. Luxol fast staining was performed. The expression of ionized calcium adaptor protein( Iba-1) and glial fibrillary acidic protein( GFAP) in the basal ganglia of rats was determined by immunofluorescence staining. The expression of myelin basic protein( MBP),interleukin-1( IL-1),IL-6 and tumor necrosis factor-α( TNF-α) in basal ganglia of rats was measured by Blot method. Results Compared with those in normal conrol group and those in sham operation group,the digging and social ability of rats in cerebral ischemia group were significantly decreased( P<0. 05). The basal ganglia area showed obvious myelin sheath depletion,and the number of Iba-1 and GFAP positive astrocytes was higher( P<0. 05). The level of MBP was significantly lower( P<0. 05),and the levels of IL-1,IL-6 and TNF-α were significantly higher( P<0. 05). Compared with cerebral ischemia group,the digging ability increased significantly( P< 0. 05),the number of Iba-1 and GFAP-positive astrocytes was decreased( P<0. 05),the level of MBP was increased( P<0. 05),and the levels of IL-1 and IL-6 were decreased in the swimming group. There was no significant difference in TNF-α( P<0. 05). Conclusions Aerobic exercise might decrease the chronic inflammation of chronic cerebral ischemia in the elderly rats with CSVD by reducing the activation of microglia in the basal ganglia and increasing the regeneration of myelin sheath.
Objective To observe the effects of aerobic exercise on the indifferent behavior induced by long-term chronic cerebral ischemia in the elderly rats with cerebral small-vessel disease( CSVD),and to invetstigate the possible neuroprotective mechanism. Methods Forty-eight adult male Sprague-Dawley rats were randomly divided into normal control group, sham-operated group( swimming training for 4 weeks without surgery),cereral ischemia group [receiving bilateral carotid artery ligation( BCCAO) only] and swimming group( receiving BCCAO and swimming training for 4 weeks). Before and 8 weeks after the operation,all the rats received digging and social tests,and the indifference behaviors of the rats were evaluated. Luxol fast staining was performed. The expression of ionized calcium adaptor protein( Iba-1) and glial fibrillary acidic protein( GFAP) in the basal ganglia of rats was determined by immunofluorescence staining. The expression of myelin basic protein( MBP),interleukin-1( IL-1),IL-6 and tumor necrosis factor-α( TNF-α) in basal ganglia of rats was measured by Blot method. Results Compared with those in normal conrol group and those in sham operation group,the digging and social ability of rats in cerebral ischemia group were significantly decreased( P<0. 05). The basal ganglia area showed obvious myelin sheath depletion,and the number of Iba-1 and GFAP positive astrocytes was higher( P<0. 05). The level of MBP was significantly lower( P<0. 05),and the levels of IL-1,IL-6 and TNF-α were significantly higher( P<0. 05). Compared with cerebral ischemia group,the digging ability increased significantly( P< 0. 05),the number of Iba-1 and GFAP-positive astrocytes was decreased( P<0. 05),the level of MBP was increased( P<0. 05),and the levels of IL-1 and IL-6 were decreased in the swimming group. There was no significant difference in TNF-α( P<0. 05). Conclusions Aerobic exercise might decrease the chronic inflammation of chronic cerebral ischemia in the elderly rats with CSVD by reducing the activation of microglia in the basal ganglia and increasing the regeneration of myelin sheath.
引文
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[15] Marner L,Nyengaard J R,Tang Y,et al. Marked loss of myelinated nerve fibers in the human brain with age[J]. J Comp Neurol,2003,462(2):144-152.
[2] Baumann A,Moreira CG,Morawska MM,et al. Preliminary evidence of apathetic-like behavior in aged vesicular monoamine transporter 2 deficient mice[J]. Front Hum Neurosci,2016,10:587.
[3] Arakawa H,Arakawa K,Deak T. Sickness-related odor communication signals as determinants of social behavior in rat:a role for inflammatory processes[J]. Horm Behav,2010,57(3):330-341.
[4] Haroutunian V,Katsel P,Roussos P,et al. Myelination,oligodendrocytes,and serious mental illness[J]. Glia,2014,62(11):1856-1877.
[5] Miyamoto N, Tanaka R, Shimura H, et al.PhosphodiesteraseⅢinhibition promotes differentiation and survival of oligodendrocyte progenitors and enhances regeneration of ischemic white matter lesions in the adult mammalian brain[J]. J Cereb Blood Flow Metab,2010,30(2):299-310.
[6] Hillman CH,Erickson KI,Kramer AF. Be smart,exercise your heart:exercise effects on brain and cognition[J]. Nat Rev Neurosci,2008,9(1):58-65.
[7] Deacon RM. Burrowing in rodents:a sensitive method for detecting behavioral dysfunction[J]. Nature Protocols,2006,1(1):118-121.
[8] Arakawa H,Arbkawa K,Deak T. Sickness-related odor communication signals as determinants of social behavior in rat:a role for inflammatory processes[J]. Horm Behav,2010,57(3):330-341.
[9] Miyamoto N, Tanaka R, Shimura H, et al.PhosphodiesteraseⅢinhibition promotes differentiation and survival of oligodendrocyte progenitors and enhances regeneration of ischemic white matter lesions in the adult mammalian brain[J]. J Cereb Blood Flow Metab,2010,30(2):299-310.
[10] Gons RA,Tuladhar AM,de Laat KF, et al. Physical activity is related to the structural integrity of cerebral white matter[J]. Neurology,2013,81(11):971-976.
[11] Sun J,Fang Y,Chen T,et al. WIN55,212-2 promotes differentiation of oligodendrocyte precursor cells and improve remyelination through regulation of the phosphorylation level of the ERK 1/2 via cannabinoid receptor 1 after stroke-induced demyelination[J]. Brain Research,2013,1491:225-235.
[12] Praet J,Guglielmetti C,Berneman Z,et al. Cellular and molecular neuropathology of the cuprizone mouse,model:clinical relevance for multiple sclerosis[J]. Neurosci Biobehav Rev,2014,47:485-505.
[13] Miron VE,Boyd A,Zhao JW,et al. M2 microglia and macrophages drive oligodendrocyte differentiation during CNS remyelination[J]. Nat Neurosci,2013,16(9):1211-U75.
[14] Kohman RA,Deyoung EK,Bhattacharya TK,et al. Wheel running attenuates microglia proliferation and increases expression of a proneurogenic phenotype in the hippocampus of aged mice[J]. Brain Behav Immun,2012,26(5):803-810.
[15] Marner L,Nyengaard J R,Tang Y,et al. Marked loss of myelinated nerve fibers in the human brain with age[J]. J Comp Neurol,2003,462(2):144-152.