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

• Published in: Neurobiology of disease Vol. 34; no. 2; pp. 340 - 350
• Main Authors: Atifi-Borel, Michèle El, Buggia-Prevot, Virginie, Platet, Nadine, Benabid, Alim-Louis, Berger, François, Sgambato-Faure, Véronique
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.05.2009; Elsevier
• Subjects: 6-hydroxydopamine; Animals; Cell Proliferation - drug effects; Corpus Striatum - drug effects; Corpus Striatum - metabolism; Corpus Striatum - physiopathology; Dopamine Agents - pharmacology; Drug Administration Schedule; Dyskinesia; Gene Expression Profiling; Gene Expression Regulation - drug effects; Gene Expression Regulation - genetics; In Situ Hybridization; Levodopa - pharmacology; Male; Microarray; Nerve Regeneration - drug effects; Nerve Regeneration - genetics; Neurogenesis - drug effects; Neurogenesis - genetics; Neurology; Neuronal Plasticity - drug effects; Neuronal Plasticity - genetics; Neurotoxins; Oxidopamine; Parkinson's disease; Parkinsonian Disorders - drug therapy; Parkinsonian Disorders - genetics; Parkinsonian Disorders - metabolism; Rats; Rats, Wistar; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - drug effects; RNA, Messenger - metabolism; Striatum; Transcriptome; Striatum; 6-hydroxydopamine; Parkinson's disease; Microarray; Transcriptome; Dyskinesia
• ISSN: 0969-9961; 1095-953X
• DOI: 10.1016/j.nbd.2009.02.002

Abstract 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.