Gene expression profiles of mouse striatum in control and maneb + paraquat-induced Parkinson's disease phenotype: validation of differentially expressed energy metabolizing transcripts.

Abstract

The present study was undertaken to investigate the gene expression patterns of the striatum of control and maneb + paraquat-induced Parkinson's disease (PD) phenotype in mouse to identify the differentially expressed transcripts. The animals were treated with and without maneb (30 mg/kg, i.p.) + paraquat (10 mg/kg, i.p.), twice a week, for 3, 6, and 9 weeks. The RNA was isolated from control and treated mouse striatum and reverse transcribed, and equal quantities of labeled cDNA were mixed and hybridized with mouse 15 k arrays. Comparative transcription patterns showed the time of exposure dependent alteration in the expression of several transcripts associated with various pathways. RT-PCR reconfirmed the differential expression of some energy metabolizing transcripts. The study provides maneb + paraquat-induced differential expression of many transcripts using high-density microarray approach. Few transcripts, which were previously not reported to be associated with neuronal degeneration, were also identified. The results obtained thus suggest that maneb + paraquat induce neurotoxicity in the striatum in a time of exposure dependent manner via multiple pathways and defective energy metabolism could play a critical role.