Impaired dendritic development is a common phenotype observed in primary cultured Purkinje cells expressing various SCA-causing proteins.

Abstract

Spinocerebellar ataxia (SCA) is a group of autosomal-dominantly inherited ataxia and classified into SCA1-49 by the difference of causal genes, whose mutations include polyglutamine (polyQ)-expanded and missense mutations. Purkinje cells (PCs) are neurons with highly developed dendrites and important for cerebellar functions. We have previously revealed that impaired dendritic development is observed in primary cultured PCs expressing missense mutant SCA14- and SCA21-causing proteins. We assume that various SCA-causing proteins commonly impairs dendritic development in cultured PCs. In the present study, we expressed polyQ-expanded (SCA1, 3 and 6) and missense (SCA34, 38, 41) mutant SCA-causing proteins in primary cultured PCs and evaluated their dendritic development. Cerebellar primary cultures were prepared from E16 embryos of Wistar rats and cultured for 3 weeks. SCA-causing proteins were expressed using adeno-associated viral vector. Compared with wild-type proteins, all 6 SCA-causing proteins, including polyQ-expanded and missense mutants, impaired dendritic development of primary cultured PCs. These findings indicates that impaired dendritic development of cultured PCs is induced by various SCA-causing proteins and would be a common in vitro phenotype of SCA and available for the exploration of novel SCA therapeutics.