ABSTRACT
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.