小胶质细胞在VPA孤独症模型大鼠脑增龄过程中的变化

Aging changes of microglia in brain of a model of autism rats prenatally exposed to valproic acid

目的:检测小胶质细胞在孤独症发病相关脑区的活化改变,探讨小胶质细胞在孤独症发病中的作用。方法:免疫组织化学技术检测丙戊酸盐(valproic acid sodium salt,VPA)孕鼠注射法建立的子代孤独症模型大鼠脑内小胶质细胞在不同周龄时前额叶皮层,海马及小脑中的活化改变;Western Blot检测小胶质细胞内电离钙绑定衔接分子-1(ionized calcium binding adaptor molecule-1,Iba-1)的表达。结果:小胶质细胞免疫组化染色显示:与正常组相比,VPA模型组大鼠不同脑区小胶质细胞的数量和密度增多,胞体增大、突起的长度和直径均增加,表明小胶质细胞的活化现象明显。Western Blot检测显示:孤独症VPA模型组前额叶皮层、海马、小脑内Iba-1的表达不同程度高于正常对照组(P<0.05),同样印证小胶质细胞在VPA模型组大鼠不同脑区的活化改变。结论:小胶质细胞的活化改变广泛存在于孤独症大鼠脑内,这可能是导致孤独症脑神经元发育与连结异常及脑内神经炎症病理过程的部分原因。

Objective： To examine the microglial change in the related brain regions and to explore the role of the microglial cells in the etiology of the autism. Methods： The microglial activation change in the autism related brain regions,prefrontal cortex,hippocampus and cerebellum in an autism model of rat that was the offspring of the mother rat pregnantly exposed in valproic acid sodium salt（ VPA）,was investigated by means of the immunohistochemical technique,and the expression of the ionized calcium binding adaptor molecule-1（ Iba-1） was tested via Western Blot method in the same time. Results： The microglial immunohistochemical staining results showed the microglia obvious alterations in autism relational brain regions in prefrontal cortex,hippocampus and cerebellum,including microglia number and density significant increased,size of soma enlarged and diameter of process thickened. These results provided evidence for microglial activation in autism. In addition,the results of Western Blot showed that the expression of the Iba-1 was up-regulated in the prefrontal cortex,hippocampus and cerebellum compared with normal control group（ P〈0. 05） and indicated that the microglia is over activated in the autism VPA models. Conclusion： Microglia is over activated extensively in the related brain regions of autism models of rats,and this activation might be the one of the reasons for abnormal development and connection of the neurons as well as the neuroimmune abnormalities in the brain of autism.