应用ERKO小鼠研究雌激素受体在MPTP致帕金森病模型中的作用  

Role of estrogen receptors in ERKO mice with Parkinson’s disease

作　　者：王强[1] 王宇[2] 钱文溢[2] 王军[2] 肖杭[2] 董海蓉[3] 丁海霞 

机构地区：[1]江苏大学基础医学与医学技术学院预防医学系,江苏镇江212013 [2]南京医科大学公共卫生学院神经毒理研究室,江苏南京210029 [3]南京医科大学第一附属医院神经内科,江苏南京210029 [4]南京医科大学第一附属医院老年神经内科,江苏南京210029

出　　处：《南京医科大学学报（自然科学版）》2012年第12期1641-1645,共5页Journal of Nanjing Medical University(Natural Sciences)

基　　金：国家自然科学基金(81072329);中国博士后基金(20110491450);江苏省博士后基金(1101027c);江苏省六大人才高峰(2009026);江苏大学高级人才科研启动基金(12JDG083)

摘　　要：目的:探讨雌激素受体(estrogen receptors,ERs)在帕金森病(Parkinson’s disease,PD)中的作用特点。方法:应用经典化学毒素MPTP腹腔注射制备小鼠PD模型,WT、αERKO和βERKO雄性小鼠随机分为Saline组和MPTP组,爬竿试验观察行为学改变,荧光定量PCR法检测纹状体和中脑ERα、ERβ、TH、DAT和VMAT2 mRNA表达的变化。结果:与WT相比,αERKO小鼠中多巴胺缺失程度更大,爬竿试验显示αERKO小鼠更早出现行为学异常。αERKO和βERKO小鼠中脑TH、DAT和VMAT2 mRNA表达均降低。WT小鼠MPTP染毒致PD模型后,纹状体和中脑ERαmRNA表达增加,ERβmRNA表达降低。MPTP致PD模型后,αERKO和βERKO小鼠TH和DAT mRNA表达变化情况与WT小鼠不同,βERKO小鼠VMAT2 mRNA表达变化情况与WT小鼠相同,但αERKO小鼠VMAT2 mRNA表达变化情况与WT小鼠不同。结论:ERs在黑质纹状体DA系统中有神经保护作用,ERα亚型在此过程中发挥着更重要的作用。Objective：Estrogen-mediated neuroprotection in the nigrostriatal dopamine system,depend on the estrogen receptors（ERs）,is now widely accepted.In the present study,the role of the two ERs in MPTP toxicity was investigated.Methods：Adult male wild type（WT）,ERs knock out（αERKO and βERKO） mice were treated with MPTP.To determine the degree of bradykinesia,pole test was performed.Quantitative real time PCR was used to examine selective genes of the dopaminergic system.Results：Our data demonstrated that administration of 1-methyl-4-phenyl-1,2,3,6-tetrapyridine（MPTP,11 mg / kg） to WT mice led to depletion of DA,DOPAC and HVA.The degree of DA depletion in the αERKO mice was greater than WT mice.Behavioral testing showed that MPTPinjected mice exhibited motor deficits in the pole test.After 2 days of MPTP treatment,a significant prolongation of T-LA was observed in αERKO mice.We also observed that mRNA expression of ERα was significantly increased in the striatum and midbrain in MPTP-treated animals,while the expression of ERβ decreased.The expression of tyrosine hydroxylase（TH）,dopamine transporter（DAT） and vesicular monoamine transporter subtype 2（VMAT2） mRNA were decreased in αERKO and βERKO mice.The downregulation of TH and DAT mRNAs by MPTP in the midbrain acted on both ERα and ERβ,whereas MPTP treatment lead to decreased mRNA expression of VMAT2 via ERα.Conclusion：Our results suggested that estrogen acting via ERs is an important regulative factor for the nigrostriatal dopamine system,ERα may play a more significant role.

关 键 词：雌激素受体 基因敲除小鼠 帕金森病 

分 类 号：R742.5[医药卫生—神经病学与精神病学]