Transcriptome Analysis of Rotenone Induced Neurotoxicity in Enriched Rat Primary Ventral Mesencephalic Neurons

                                       http://austinpublishinggroup.com/neurology-neurosciences/

Rotenone induced neurotoxicity is being widely investigated in relation to Parkinson’s Disease (PD). However the crucial molecular mechanisms involved in rotenone induced PD still remains elusive. This report details the transcriptome changes on rotenone treatment in enriched rat primary ventral mesencephalic neurons through microarray analysis. Transcriptome analysis had yielded 705 up-regulated genes and 2415 down-regulated genes. This data was further validated by quantitative real time PCR analysis. To further refine this data, association rule mining was used and a gene interaction network among 53 genes was developed. Functional characterization of the top 25 scored genes in the network was done using panther database. Interestingly TNF was the highest scored gene among them and found to be significantly down regulated on rotenone treatment. Along with TNF other inflammation related genes like Il1b, Itpr3 and TNFR2 were also significantly down-regulated on rotenone treatment. These observations suggest that down regulation of neuronal TNF might be a critical cause leading to cellular death via TNFR2, Il1b mediated Pi3Kinase pathway in rotenone induced neurotoxicity. Further investigation in this neuronal TNF related pathways may give novel therapeutic approaches in treatment of PD.

In-Vitro/In-Vivo treatments with rotenone are known to induce certain features of Parkinson Disease (PD). Dopaminergic neurodegeneration in substantianigra pars compacta of Ventral Mesencephalic (VM) brain region is the hall mark feature of PD. Rotenone, besides affecting mitochondrial function was also reported to be affecting a variety of cellular processes like cytoskeleton stability, inflammation, oxidative stress and apoptosis. All these observations were made using directed approaches studying few of the genes involved in those specific pathways. Microarray analysis of whole transcriptome is an alternative approach for identifying key genes and pathways that might not be feasible through single-gene studies. Enriched rat primary VM neurons were well characterized and studied in co-relation with rotenone induced neurotoxicity. In the present study primary VM neurons were analyzed for changes in their genome expression upon rotenone treatment using microarray analysis along with Association Rule Mining (ARM) for discovering the relationship among genes in a large dataset.