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性别因素对GRK5缺陷小鼠AD样病理改变的影响
引用本文:李龙宣,唐荣华,William Z.Suo.性别因素对GRK5缺陷小鼠AD样病理改变的影响[J].中国组织化学与细胞化学杂志,2008,17(5):490-496.
作者姓名:李龙宣  唐荣华  William Z.Suo
作者单位:1. 华中科技大学同济医学院同济医院神经科,武汉 430030;广东医学院附属医院神经科,湛江 524001
2. 华中科技大学同济医学院同济医院神经科,武汉 430030;
3. Lab.for Alzheirner Disease&Aging Res,VA Med Center,Kansas Cjfy,MO 64128;Departroents of Neurology,and Molecular & Integrative Physiology;Univ.of Kansas MecL Center,Kansas City,KS 66170,USA
摘    要:目的性别在阿尔茨海默病(AD)的发病中是一不容忽视的危险因素。研究揭示G蛋白偶联受体(GPCRs)激酶5(GRK5)缺陷引起的相关GPCRs脱敏障碍在早期AD病理发生机制中具有重要作用,而且GRK5敲除/缺陷(GRK5KO)小鼠表现出早期AD样病理特征和短时期记忆功能损害。但这种病理变化在不同性别间有无差异,目前不得而知。本研究旨在探讨GRK5KO小鼠出现的AD样病理变化是否存在性别差异。方法用Campbell-Switzer银染来观察老龄GRK5KO小鼠海马内肿胀轴突的病理变化;Western blotting检测海马内突触蛋白水平和数个胆碱能标记物的变化;同时对上述改变在不同性别间进行深入比较。结果雌性GRK5KO小鼠海马内肿胀轴突数目比雄性小鼠高出2.5倍;而且雌性GRK5KO小鼠海马内数个突触蛋白水平比雄性小鼠显著减低。双因素方差分析显示性别和GRK5缺陷双因素之间呈显著协同效应,共同促进了雌性GRK5KO小鼠轴突缺陷和部分突触蛋白水平的降低。另外,胆碱能标记物检测显示,雌性GRK5KO小鼠毒蕈碱受体2、4以及乙酰胆碱酯酶水平较雄性小鼠显著增高。结论在促进早期AD病理发生的过程中,GRK5缺陷和性别双因素表现出协同效应,共同加剧了雌性GRK5KO小鼠脑内的AD样病理改变。

关 键 词:性别  阿尔茨海默病  G蛋白偶联受体激酶5  轴突缺陷  突触退变

THE EFFECT OF GENDER FACTOR ON THE ALZHEIMER-LIKE PATHOLOGIC CHANGES OF GRK5 DEFICIENT MICE
Li Longxuan,Tang Ronghua,William Z.Suo.THE EFFECT OF GENDER FACTOR ON THE ALZHEIMER-LIKE PATHOLOGIC CHANGES OF GRK5 DEFICIENT MICE[J].Chinese Journal of Histochemistry and Cytochemistry,2008,17(5):490-496.
Authors:Li Longxuan  Tang Ronghua  William ZSuo
Institution:Li Longxuan1,5,Tang Ronghua1,William Z.Suo2,3,4(1Department of Neurology,Tongji Hospital,Tongji Medical College,Huazhong University of Science , Technology,Wuhan 430030,China,2Lab.for Alzheimer Disease & Aging Res.,VA Med.Center,Kansas City,MO 64128,Departments of 3Neurology,, 4Molecular & Integrative Physiology,Univ.of Kansas Med.Center,KS 66170,USA,5Department of Neurology,Affiliated Hospital ofGuangdong Medical College,Zhanjiang 524001,China)
Abstract:Objective Recent studies suggested that G protein-coupled receptor kinase 5(GRK5) deficiency plays a significant role in early Alzheimer's disease(AD) pathogenesis,and that GRK5 knockout/deficiency(GRK5KO) mouse displays an early Alzheimer-like cognitive deficit associated with increased hippocampal axonal defects and synaptic degenerative changes.Gender is known to play a role in AD,with female showing more extensive pathologic changes in brain as compared to male.Although GRK5 deficiency is linked to AD,i...
Keywords:Gender  Alzheimer disease  GRK5  Axonal defect  Synaptic degeneration  
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