Big data analysis of whole striatum transcriptome after L-DOPA or Pramipexole treatment in a rat model of Parkinson's disease

ANDREA CECILIA CURA; GIMENA GÓMEZ; ENRICO GLAAB; MAREK OSTASZEWSKI; JORGE GONÇALVEZ; OSCAR S. GERSHANIK; IRENE RE. TARAVINI

Congreso; XXXII Congreso Anual SAN 2017; 2017

L-DOPA is the most effective treatment of Parkinson´s disease (PD), but it frequently produces response fluctuations and abnormal involuntary movements after long-term treatment. Pramipexole is a D2/D3 dopamine receptor agonist which has a lower efficacy but also a lower propensity to induce motor complications. Therefore, it is likely that different molecular changes underlie these specific pharmacological responses. Transcriptomic technologies have aided large-scale research to elucidate the link between a specific gene or a cluster of genes and a particular biological mechanism. We used DNA microarray technology to assess whether the striatal gene expression profiles of hemiparkinsonian rats treated with L-DOPA or Pramipexole show statistically significant differences. To produce a model of early PD, rats received a unilateral injection of 6-OHDA in the striatum and were treated with L-DOPA or Pramipexole for three weeks. Differences in gene expression were assessed using the empirical Bayes moderated t-statistic. Overall, more than a thousand of genes were differentially expressed. The PD map of the University of Luxembourg was used as an exploratory tool to point out the localization of differentially expressed genes within biological pathways and compartments refining gene selection. This analysis will reveal new genetic striatal networks possibly contributing to the therapeutic effects of the most common treatments for PD.