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.
El Atifi-Borel
Michèle
M
Institut National de la Santé et de la Recherche Médicale, Grenoble, France.
Buggia-Prevot
Virginie
V
Platet
Nadine
N
Benabid
Alim-Louis
AL
Berger
François
F
Sgambato-Faure
Véronique
V
D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D015259:Dopamine Agents / Q000494:pharmacology; D004334:Drug Administration Schedule; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000235:genetics; D017403:In Situ Hybridization; D007980:Levodopa / Q000494:pharmacology*; D008297:Male; D009416:Nerve Regeneration / Q000187:drug effects / Q000235:genetics; D055495:Neurogenesis / Q000187:drug effects / Q000235:genetics; D009473:Neuronal Plasticity / Q000187:drug effects / Q000235:genetics; D009498:Neurotoxins; D016627:Oxidopamine; D020734:Parkinsonian Disorders / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction
D015259:Dopamine Agents; D009498:Neurotoxins; D012333:RNA, Messenger; D007980:Levodopa; D016627:Oxidopamine