VPA诱导的自闭症青年小鼠海马中PLCγ1/IP3R/CaMKⅡ蛋白表达和树突棘密度的变化

Changes of PLCγ1/IP3R/CaMKⅡprotein expression and dendritic spine density in hippocampus of VPA-induced autistic young mice

目的探讨丙戊酸钠(VPA)诱导的自闭症模型小鼠大脑海马区磷脂酶C-γ1(PLCγ1)/肌醇三磷酸受体(IP3R)/钙调蛋白依赖性激酶Ⅱ(CaMKⅡ)表达的改变和树突棘密度的异常。方法 C57孕小鼠于孕10、12 d分别腹腔注射丙戊酸钠300 mg/kg或生理盐水,其仔鼠分别为自闭症谱系障碍模型鼠(VPA组)或正常对照鼠(CON组)。Western blot检测两组仔鼠大脑海马区PLCγ1、IP3R、CaMKⅡ和突触后致密物-95(PSD95)的表达水平。高尔基染色法检测2组仔鼠大脑海马区树突棘的变化。结果 Western blot检测结果显示:与正常对照组相比,VPA组小鼠大脑海马区PLCγ1,IP3R,CaMKⅡ和PSD95的表达均下降(P<0.01)。高尔基染色结果显示:与正常对照组相比,VPA组小鼠大脑海马区树突棘密度减少(P<0.01)。结论 VPA诱导的自闭症模型小鼠大脑海马区的PLCγ1/IP3R/CaMKⅡ表达下降,同时伴随着海马CA1区锥体神经元树突棘密度降低,PSD95的表达减少。

Objective To investigate expression changes of phospholipase C-γ1(PLCγ1)/inositol triphosphate receptor(IP3R)/calmodulin-dependent kinaseⅡ(CaMKⅡ)and density of dendritic spine in the hippocampus of autism model mice induced by sodium valproate(VPA).Methods Pregnant C57 mouse was given intraperitoneal injection of 300 mg/kg VPA or same volume of normal saline at the 10th and 12th days of gestation.The offspring exposed to VPA or saline during gestation were identified as autism spectrum disorder mice(VPA group)or normal control mice(CON group).Western blotting was used to detect the expression levels of PLCγ1,IP3R,CaMKⅡand post-synaptic dense-95(PSD95)in the hippocampus of the 2 groups.Golgi staining was employed to observe the changes in dendritic spines in the hippocampus of the offspring mice.Results Western blotting showed that the expression levels of PLCγ1,IP3R,CaMKⅡand PSD95 were decreased in the VPA group than the normal control group(P<0.01).Golgi staining indicated that compared with the normal control group,the density of dendritic spines in the hippocampus of VPA mice was reduced(P<0.01).Conclusion In the hippocampus of VPA induced autism mice,the expression of PLCγ1/IP3R/CaMKⅡand PSD95 and the dendritic spine density of pyramidal neurons in hippocampal CA1 are all decreased compared with the normal control mice.