Contrasting gene expression patterns induced by levodopa and pramipexole treatments in the rat model of Parkinson's disease

TARAVINI, IRENE R; LARRAMENDY, CELIA; GOMEZ, GIMENA; SABORIDO, MARIANO D; SPAANS, FLOOR; FRESNO, CRISTOBAL; GONZALEZ, GERMÁN; FERNÁNDEZ, ELMER ANDRÉS; MURER, MARIO G; GERSHANIK, OSCAR

NEUROPHARMACOLOGY

PERGAMON-ELSEVIER SCIENCE LTD

Año: 2015

0028-3908

Whether the treatment of Parkinson´s disease has to be initiated with levodopa or a D2 agonist like pramipexole remains debatable. Levodopa is more potent against symptoms than D2 agonists, but D2 agonists are less prone to induce motor complications and may have neuroprotective effects. Although regulation of plastic changes in striatal circuits may be the key to their different therapeutic potential, the gene expression patterns induced by de novo treatments with levodopa or D2 agonists are currently unknown. By studying the whole striatal transcriptome in a rodent model of early stage Parkinson´s disease, we have identified the gene expression patterns underlying therapeutically comparable chronic treatments with levodopa or pramipexole. Despite the overall relatively small size of mRNA expression changes at the level of individual transcripts, our data show a robust and complete segregation of the transcript expression patterns induced by both treatments. Moreover, transcripts related to oxidative metabolism and mitochondrial function were enriched in levodopa-treated compared to vehicle-treated and pramipexole-treated animals, whereas transcripts related to olfactory transduction pathways were enriched in both treatment groups compared to vehicle-treated animals. Thus, our data reveal the plasticity of genetic striatal networks possibly contributing to the therapeutic effects of the most common initial treatments for Parkinson´s disease, suggesting a role for oxidative stress in the long term complications induced by levodopa and identifying previously overlooked signaling cascades as potentially new therapeutic targets.