摘要
目的探讨3种不同帕金森病(Parkinson disease,PD)动物模型黑质、纹状体和海马中磷酸化α-synuclein(S129)[以下简称为p-α-syn(S129)]和天冬酰胺内切酶(asparagine endopeptidase,AEP)特异性切割产生的tauN368片段的表达水平。方法建立慢性1-甲基-4-苯基-1,2,3,6-四羟吡啶(MPTP)诱导的PD小鼠模型(n=10)、鱼藤酮诱导的小鼠PD模型(n=10)以及鱼藤酮诱导的大鼠PD模型(n=10)共3种模型,每种模型均设立对照组(n=10)。采用酪氨酸羟化酶(tyrosine hydroxylase,TH)免疫染色评估不同PD动物模型黑质多巴胺能神经元损伤情况,采用Western blot方法检测各组动物中脑黑质、纹状体、海马p-α-syn(S129)和tauN368的表达。结果 3种PD动物模型中脑黑质致密部TH阳性神经元数目均较对照组明显减少,提示造模成功。Western blot检测结果显示,MPTP诱导的小鼠PD模型黑质、纹状体及海马tauN368表达均较对照组升高(P<0.05),黑质和海马p-α-syn(S129)表达无统计学差异(P>0.05);鱼藤酮诱导的小鼠PD模型黑质及纹状体p-α-syn(S129)和tauN368表达均较对照组增加(P<0.05),而海马p-α-syn(S129)和tauN368表达与对照组比较均未见统计学变化(P>0.05);鱼藤酮诱导的大鼠PD模型黑质、纹状体及海马p-α-syn (S129)表达较对照组增加(P<0.05),而黑质和海马tauN368的表达无统计学差异(P>0.05)。结论鱼藤酮诱导的小鼠PD模型黑质和纹状体同时存在tauN368和p-α-syn(S129)的差异性表达,提示该模型可能是研究PD发病中tauN368和α-synuclein相互作用机制的理想动物模型。
Objective To reveal the expressions of p-α-synuclein(S129)and tauN368 fragment cleaved by asparagine endopeptidase(AEP)in three animal models of Parkinson s disease(PD).Methods We established three animal models of PD:MPTP induced mice model,rotenone induced mice model,and rotenone induced rat model.Control groups(n=10)were established for each animal model,and the animals in control groups were given the equal volume of vehicles with the same methods of administration.Tyrosine hydroxylase immunostainings were performed to evaluate MPTP and rotenone induced neurotoxicity on dopaminergic neurons of substantia nigra.Western blot was used to detect the expression of tauN368 and p-α-synuclein(S129)in substantia nigra,striatum and hippocampus of the three PD models.Results Decreased numbers of TH positive neurons in the substantia nigra of these three PD models were demonstrated.Western blot analysis showed that the expressions of tau N368 in the substantia nigra,striatum and hippocampus of MPTP induced PD model was higher than that of the control group(P<0.05),there was no significant difference in the expression of p-α-synuclein(S129)in the substantia nigra and hippocampus compared with the control group(P>0.05).The expressions of p-α-synuclein(S129)and tauN368 in the substantia nigra and striatum of the rotenone induced mouse PD model were higher than those of the control group(P<0.05),and there was no significant difference in the expressions of p-α-synuclein(S129)and tauN368 of hippocampus compared with the control group(P>0.05).The expressions of p-α-synuclein(S129)in the substantia nigra,striatum and hippocampus of rotenone induced rat PD model was higher than that of the control group(P<0.05).There was no significant difference in the expression of tauN368 in the substantia nigra and hippocampus compared with the control group(P>0.05).Conclusions The differential expressions of tauN368 and p-α-synuclein(S129)were demonstrated in the substantia nigra and striatum of the rotenone induced mouse PD model,indicating that this model is an optimal model for investigating the interaction between the two proteins.
作者
聂淑科
马凯
陈贵勤
张振涛
曹学兵
NIE Shuke;MA Kai;CHENG Guiqin;ZHANG Zhentao;CAO Xuebing(Department of Neurology,Renmin Hospital of Wuhan University,Wuhan Hubei 430066,China)
出处
《中国神经免疫学和神经病学杂志》
CAS
北大核心
2018年第5期341-346,共6页
Chinese Journal of Neuroimmunology and Neurology
基金
国家自然科学基金青年项目(No.81701257)
作者简介
通信作者:聂淑科,Email:nieshuke200554@163.com
