In vivo gene delivery to proliferating cells in the striatum generated in response to a 6-hydroxydopamine lesion of the nigro-striatal dopamine pathway

Abstract

The degeneration of neurons in the mammalian brain is commonly associated with the division of cells located in the damaged area. The aim of the present study has been to characterise the phenotype of newly born cells in the striatum of adult rats following 6-hydroxydopamine lesion of the nigro-striatal pathway. Newborn cells were identified through labelling with either bromodeoxyuridine or retrovirus encoding green fluorescence protein. We report here that the overwhelming majority of these cells have glial characteristics. In order to promote the generation of new neurons we retrovirally introduced either the noggin or neurogenin2 genes into newborn cells following the 6-hydroxydopamine lesion. Transduction with neurogenin2 resulted in the production of cells resembling neuroblasts, however these cells did not appear to survive. Noggin transduction did not result in the generation of new neurons, but interestingly, greatly increased the number of oligodendrocytes generated from newborn cells.

Keywords

• Proliferation
• Retrovirus
• Noggin
• Neurogenin2
• Parkinson's disease