酪氨酸羟化酶在C型尼曼-匹克病小鼠小脑中的异常表达

ABNORMAL EXPRESSION OF TYROSINE HYDROXYLASE IN THE CEREBELLUM OF NIEMANN-PICK TYPE C MICE

目的 探讨C型尼曼 匹克病 (NPC)小脑中酪氨酸羟化酶 (TH)异常表达的时间、部位及其与临床表现的关系。 方法 应用TH抗体 ,对不同周龄NPC小鼠和正常小鼠的脑组织切片进行免疫组织化学染色 ,部分相邻切片以抗维生素D依赖性钙结合蛋白抗体染色。 结果 1～ 3周NPC小鼠小脑的浦肯野细胞 (PC)未见明显减少 ,TH染色阴性。 5周时PC开始减少 ,8～ 11周期间PC显著丢失 ,但小脑蚓小结和蚓垂有较多的PC存活。 8周后 ,部分存活的PC及其树突树出现TH免疫反应。其轴突局部球形膨大 ,树突不规则 ,弯曲、断裂、局部膨大 ,树突树萎缩。 结论 NPC1基因突变引起小脑PC严重丢失 ,存活的PC有形态改变和异常基因活动 ,提示其功能不正常 。

Objective To investigate the time, location and relationship to clinical manifestation of abnormal expression of tyrosine hydroxylase(TH) in the cerebellum of Niemann\|Pick type C disease (NPC). Methods Immunohistochemical staining was applied, by using antibodies to TH, to brain sections from NPC and normal mice of various ages. Some adjacent sections were stained for calbindin D28k. Results There was no marked decrease in number of cerebellar Purkinje cells(PC), which were negatively stained for TH, in the NPC mice aged 1\|3 weeks. The PC were decreased in number starting from week 5. During postnatal weeks 8\|11, PC were significantly lost, but considerable number of PC in the nodulus and uvula vermis survived. Some survived PC and their dendritic trees were TH immunoreactive after week 8. These PC showed axonal spheroids and irregular dendrites that were bent, broken, locally enlarged or atrophied. Conclusion Mutation of NPC1 gene induces severe loss of cerebellar PC and survived PC have been damaged morphologically and show abnormal gene activity. These may be the pathogenic basis of movement disorders of NPC.