De novo and long-term L-Dopa induce both common and distinct striatal gene profiles in the hemiparkinsonian rat

We compared for the first time the effects of de novo versus long-term L-Dopa treatment inducing abnormal involuntary movement on striatal gene profiles and related bio-associations in the 6-hydroxydopamine rat model of Parkinson's disease. We examined the pattern of striatal messenger RNA expression over 4854 genes in hemiparkinsonian rats treated acutely or chronically with L-Dopa, and subsequently verified some of the gene alterations by in situ hybridization or real-time quantitative PCR. We found that de novo and long-term L-Dopa share common gene regulation features involving phosphorylation, signal transduction, secretion, transcription, translation, homeostasis, exocytosis and synaptic transmission processes. We also found that the transcriptomic response is enhanced by long-term L-Dopa and that specific biological alterations are underlying abnormal motor behavior. Processes such as growth, synaptogenesis, neurogenesis and cell proliferation may be particularly relevant to the long-term action Of L-Dopa. (C) 2009 Elsevier Inc. All rights reserved.