Gene expression profiles of mouse striatum in control and maneb + paraquat-induced Parkinson's disease phenotype: validation of differentially expressed energy metabolizing transcripts.
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.
Patel
Suman
S
Industrial Toxicology Research Centre , Mahatma Gandhi Marg, Lucknow, 226 001, India.
Singh
Kavita
K
Singh
Seema
S
Singh
Mahendra Pratap
MP
D000818:Animals; D015153:Blotting, Western; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004195:Disease Models, Animal; D004734:Energy Metabolism / Q000235:genetics*; D005659:Fungicides, Industrial / Q000494:pharmacology; D020869:Gene Expression Profiling; D006540:Herbicides / Q000494:pharmacology; D008297:Male; D008344:Maneb / Q000494:pharmacology*; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D010269:Paraquat / Q000494:pharmacology*; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics
D005659:Fungicides, Industrial; D006540:Herbicides; D012333:RNA, Messenger; D008344:Maneb; D010269:Paraquat