Gene expression profiles of reactive astrocytes in dopamine-depleted striatum

We have used cDNA array analysis to examine the expression of genes in reactive astrocytes of dopamine-depleted striatum of rats in vivo, an animal model for Parkinson disease, compared to those from control striatum. The striatum of both normal adult rats and rats whose substantia nigra had been lesioned with 6-hydroxydopamine was removed one week following lesion. After fixing the tissue in RNAlater, individual astrocytes, isolated directly from dissociated striatum and confirmed to be astocytes by expression of glial fibrillary acidic protein (GFAP) mRNA using single cell RT-PCR, were used as the source of mRNA. Co-localization of GFAP with either of 2 antibodies known to label only reactive astrocytes in vivo confirmed that virtually all astrocytes in the lesioned striatum were reactive. The analysis has identified 29 genes whose expression is turned on or enhanced in dopamine-depleted striatal astrocytes and 2 whose expression is decreased. In situ hybridization was used to confirm the localization of 8 of these genes to astrocytes: these included GDNF, NGF, bFGF, TNF-alpha, MIP-1alpha, c-jun, Fra-1 and Fra-2. Understanding these gene differences that occur in astrocytes in response to dopamine depletion should enhance our ability to promote recovery from the injury.