Abstract
Viral-vector-mediated gene expression in a specific subset of developing cells is a useful approach for exploring nervous system development. Here we attempted to transduce developing Purkinje cells by injecting lentiviral vectors into neonatal rat cerebellum. We injected lentivectors expressing GFP into the cerebellar cortex of postnatal day 0 (P0) pups, and found robust GFP expression in Purkinje cells three days after the injection (P3). Electrophysiological analysis of P21-P23 Purkinje cells infected with lentiviral vectors at P0 showed no significant alteration compared with non-transduced Purkinje cells. Consistently, rotarod performance of P21-P23 rats treated neonatally with lentiviral vectors was very similar to that of non-treated littermates. These results suggest that infection of lentiviral vectors does not influence viability, or morphological or functional maturation of developing Purkinje cells. Interestingly, unlike mature granule cells, granule cell precursors in the external granular layer were efficiently transduced. Thus, the lentiviral vector is a versatile tool for the delivery of a foreign gene into developing neurons in the cerebellar cortex without significant influence on the process of their development, and can be used to unravel roles of genes involved in cerebellar development as well as gene therapy vector, for example, against congenital cerebellar diseases. [J Physiol Sci. 2008;58 Suppl:S127]
