G-CSF对帕金森病小鼠运动能力和黑质纹状体神经元的影响

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英文篇名：Effects of granulocyte colony-stimulating factor on nigrostriatal neurons in the mouse model of Parkinson's disease 作者：张丹丹 ; 张宇新 ; 张乘云 ; 郭森 ; 崔海鹏 ; 贾桦 英文作者：Zhang Dandan;Zhang Yuxin;Zhang Chengyun;Guo Sen;Cui Haipeng;Jia Hua;Department of Human Anatomy and Embryology,College of Basic Medical Sciences,Ningxia Medical University;Department of Human Anatomy,College of Basic Medical Sciences,North China University of Science and Technology;Chengde Medical University, Department of Human Anatomy;Chengde Medical University, Department of Pathophysiology; 关键词：帕金森病 ; 1-甲基-4-苯基-1 ; 2 ; 3 ; 6-四氢吡啶 ; 粒细胞集落刺激因子 ; 酪氨酸羟化酶 ; 小鼠 英文关键词：Parkinson disease(PD);;1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP);;granulocyte colony stimulating factor(G-CSF);;tyrosine hydroxylase(TH);;mouse 中文刊名：SJJP 英文刊名：Chinese Journal of Neuroanatomy 机构：宁夏医科大学基础医学院人体解剖与组织胚胎学系;华北理工大学基础医学院人体解剖学教研室;承德医学院人体解剖学教研室;承德医学院病理生理学教研室; 出版日期：2019-01-31 出版单位：神经解剖学杂志 年：2019 期：v.35 基金：宁夏自然科学基金(2018AAC03067) 语种：中文; 页：SJJP201901001 页数：7 CN：01 ISSN：61-1061/R 分类号：7-13

摘要

目的:探讨粒细胞集落刺激因子(G-CSF)对1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)所致小鼠帕金森病(PD)模型中脑黑质致密部(SNpc)及纹状体(STR)多巴胺(DA)能神经元的影响。方法:正常健康雄性C57BL/6J小鼠随机分为对照组、MPTP组及MPTP+G-CSF组,采用腹腔注射MPTP法制作小鼠PD模型,MPTP+G-CSF组于最后一次MPTP注射后再腹腔注射G-CSF。爬杆实验观察小鼠的行为学改变;尼氏染色技术观察各组小鼠黑质致密部神经元数量及形态学变化;免疫组织化学法检测酪氨酸羟化酶(TH)在各组小鼠中脑黑质致密部及纹状体的表达; Western Blot法检测各组小鼠中脑TH蛋白的表达量。结果:与对照组相比,MPTP组小鼠较对照组爬杆用时显著延长(P <0. 05),尼氏染色显示黑质致密部神经元数量显著减少(P <0. 05),黑质致密部、纹状体TH表达量显著减少(P <0. 05); MPTP+G-CSF组较MPTP组爬杆用时显著缩短(P <0. 05),神经元丢失减少(P <0. 05),神经元形态较完整;与MPTP组比较,MPTP+G-CSF组黑质致密部、纹状体TH表达水平显著增高(P <0. 05)。结论:G-CSF能够改善PD小鼠运动功能,减少黑质致密部多巴胺能神经元丢失,增加TH表达水平。
        Objective: To observe the effects of granulocyte colony stimulating factor( G-CSF) on the dopaminergic neurons( DA) of the substantia nigra pars compacta( SNpc) and striatum( STR) in the mouse Parkinson's disease( PD)model of the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine( MPTP). Methods: The normal healthy male C57BL/6J mice were randomly divided into the saline control group,the MPTP-exposed group and the MPTP-exposed group followed by G-CSF treatment. The mice of PD model were intraperitoneally injected with MPTP,and the MPTP + G-CSF group was injected with G-CSF after the final MPTP injection. The behavioral changes of mice were observed by Pole Test. Staining of Nissl was then used to observe the number and morphological changes of neurons in SNpc in each group. Additionally,the expression of tyrosine hydroxylase( TH) in SNpc and STR of mice in each group was detected by immunohistochemistry,and the expression of TH protein in the midbrain of mice in each group was detected by Western Blot. Results: Compared with the saline control group,the time to reach the floor in group MPTP were significantly decreased in reaching thefloor( P < 0. 05). Staining of Nissl showed that the number of neurons in SNpc was significantly reduced( P < 0. 05).The expression of TH in SNpc and STR was significantly reduced( P < 0. 05); compared with group MPTP,the time of reaching in group MPTP + G-CSF was significantly shortened( P < 0. 05),neuron loss was reduced( P < 0. 05),and the morphology of neurons was relatively complete; compared with group MPTP,the MPTP + G-CSF group showed a significantly higher expression level of TH in SNpc and STR( P < 0. 05). Conclusion: G-CSF can improve the motor function of PD mice,reduce the loss of DA in the SNpc,and increase the expression level of TH.

引文

[1]Khan AU,Akram M,Daniyal M,et al.Awareness and current knowledge of Parkinson disease:a neurodegenerative disorder[J].Int J Neurosci.2018:1-39.DOI:10.1080/00207454.2018.1486837.
    [2]Huang D,Xu J,Wang J,et al.Dynamic changes in the nigrostriatal pathway in the MPTP mouse model of Parkinson’s disease[J].Parkinson’s Disease,2017,2017::9349487.DOI:10.1155/2017/9349487.
    [3]Johnson ME,Salvatore MF,Maiolo SA et al.Tyrosine hydroxylase as a sentinel for central and peripheral tissue responses in Parkinson’s progression:evidence from clinical studies and neurotoxin models[J].Prog Neurobiol,2018,165-167:1-25.DOI:10.1016/j.pneurobio.2018.01.002.
    [4]Qamar MA,Sauerbier A,Politis M,et al.Presynaptic dopaminergic terminal imaging and non-motor symptoms assessment of Parkinson’s disease:evidence for dopaminergic basis[J].NPJ Parkinson’s Disease,2017,3:1-20.DOI:10.1038/s41531-016-0006-9.
    [5]Demetri GD,Griffin JD.Granulocyte colony-stimulating factor and its receptor[J].Blood,1991,78(11):2791-808.
    [6]Khorasanizadeh M,Eskian M,Vaccaro AR,et al.Granulocyte colony-stimulating factor(G-CSF)for the treatment of spinal cord injury[J].CNS Drugs,2017,31(11):911-937.DOI:10.1007/s40263-017-0472-6.
    [7]Schneider A,Krger C,Steigleder T,et al.The hematopoietic factor G-CSF is a neuronal ligand that counteracts programmed cell death and drives neurogenesis[J].J Clin.Invest,2005,115(8):2083-2098.DOI:10.1172/JCI23559.
    [8]Azmy MS,Menze ET,Elnaga RN,et al.Neuroprotective effects of filgrastim in rotenone-induced Parkinson’s disease in rats:insights into its anti-inflammatory,neurotrophic,and antiapoptotic effects[J].Molecular Neurobiology,2018,55(8):6572-6588.DOI:10.1007/s12035-017-0855-1.
    [9]Kook YH,Ka M,Um M.Neuroprotective cytokines repress PUMAinduction in the 1-methyl-4-phenylpyridinium(MPP+)model of Parkinson’s disease[J].Biochemical&Biophysical Research Communications,2011,411(2):370-374.DOI:10.1016/j.bbrc.2011.06.151.
    [10]Cao XQ,Arai H,Ren YR,et al.Recombinant human granulocyte colony-stimulating factor protects against MPTP-induced dopaminergic cell death in mice by altering Bcl-2/Bax expression levels[J].JNeurochemistry,2010,99(3):861-867.DOI:10.1111/j.1471-4159.2006.04125.x.
    [11]Zeng XS,Geng WS,Jia JJ.Neurotoxin-induced animal models of Parkinson disease:pathogenic mechanism and assessment[J].Asn Neuro,2018,10:1-15.DOI:10.1177/1759091418777438.
    [12]Schildknecht S,Pape R,Meiser J,et al.Preferential extracellular generation of the active Parkinsonian toxin MPP+by transporter-independent export of the intermediate MPDP+[J].Antioxid Redox Signal,2015,23(13):1001-1016.DOI:10.1089/ars.2015.6297.
    [13]Xu YD,Cui C,Sun MF et al.Neuroprotective effects of loganin on MPTP-induced Parkinson’s disease mice:neurochemistry,glial reaction and autophagy studies[J].J Cell Biochem,2017,118(10):3495-3510.DOI:10.1002/jcb.26010.
    [14]Lee ST,Park JE,Kim DH,et al.Granulocyte-colony stimulating factor attenuates striatal degeneration with activating survival pathways in 3-nitropropionic acid model of Huntington’s disease[J].Brain Research,2008,1194:130-137.DOI:10.1016/j.brainres.2007.11.058.
    [15]Gibson CL,Bath PMW,Murphy SP.G-CSF reduces infarct volume and improves functional outcome after transient focal cerebral ischemia in mice[J].Journal of Cerebral Blood Flow&Metabolism2005,25(4):431-439.DOI:10.1038/sj.jcbfm.9600033.
    [16]Menzie-Suderam JM,Mohammad-Gharibani P,Modi J,et al.Granulocyte-colony stimulating factor protects against endoplasmic reticulum stress in an experimental model of stroke[J].Brain Research,2017,1682:1-13.DOI:10.1016/j.brainres.2017.12.022.
    [17]UrdzíkováL,JendelováP,GlogarováK,et al.Transplantation of bone marrow stem cells as well as mobilization by granulocyte-colony stimulating factor promotes recovery after spinal cord injury in rats[J].J Neurotrauma,2006,23(9):1379-1391.DOI:10.1089/neu.2006.23.1379.
    [18]Mu1oz-Manchado AB,Villadiego J,Romo-Madero S,et al.Chronic and progressive Parkinson’s disease MPTP model in adult and aged mice[J].J Neurochemistry,2016,136(2):373-387.DOI:10.1111/jnc.13409.
    [19]Zhao LR,Navalitloha Y,Singhal S,et al.Hematopoietic growth factors pass through the blood-brain barrier in intact rats[J].Experimental Neurology,2007,204(2):569-573.DOI:10.1016/j.expneurol.2006.12.001.
    [20]CzOnkowska A,Kohutnicka M,Kurkowska-Jastrzebska I,et al.Microglial reaction in MPTP(1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)induced Parkinson’s disease mice model[J].Neurodegeneration,1996,5(2):137-143.