CHRONOLOGICAL AND IMMUNOHISTOCHEMICAL OBSERVATIONS OF CEREBELLAR DYSPLASIA AND VERMIS DEFECT IN THE HEREDITARY CEREBELLAR VERMIS DEFECT (CVD) RAT

Hereditary cerebellar vermis defect (CVD) rats, a new neurological mut ant, developed both cerebellar vermis defect and cerebellar dysplasia. Developmental alterations in the cerebellum of the CVD rats were stud ied chronologically and immunohistochemically. The earliest architectu ral abnormality was a maldevelopment of the inferior cerebellar pedunc le from embryonic day 17 (E17), leading to an indistinct separation be tween the cerebellum and the pens. From E19, the CVD rats lacked vermi s development and, therefore, the cerebellar hemispheres were fused. A fter birth, Purkinje cells and external granule cells (EGCs) penetrate d into the pontine tissue, but retained their normal position until po stnatal day 10. Cerebellar lamination began to be disturbed due to abn ormal perivascular aggregations of the EGCs, resulting in convoluted a nd occasionally perivascular lamination. There were no Bergmann glia i n the heterotopic cerebellum of the pens, and abnormally arranged Berg mann glia were observed in the mildly disorganized cerebellar hemisphe res. Immunohistochemistry for calbindin revealed that abnormal orienta tion of the Purkinje cells might be related to the perivascular EGCs. Parvalbumin-immunopositive microneurons were seen only in the disarran ged molecular layers, and synaptophysin-immunopositive cerebellar glom eruli were present in the afflicted internal granular layers. These fi ndings suggest that perivascular EGCs may play an important role in ce rebellar dysplasia and the developmental plasticity in the altered cer ebellogenesis.