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

Neurobiology of Disease

Véronique Sgambato-Faure¹  Virginie Buggia-Prevot²  Michèle El Atifi-Borel³  Alim-Louis Benabid³  Nadine Platet³  François Berger³ 

[1] CEA-MINATEC-LETI, Clinatec, Grenoble F-38054, France;Institut National de la Santé et de la Recherche Médicale, Unité 836, Grenoble Institut des Neurosciences, Equipe Nanomédecine et Cerveau, Grenoble F-38043 cedex 09, France;Institut National de la Santé et de la Recherche Médicale, Unité 318, Grenoble F-38043 cedex 09, France;

关键词: Parkinson's disease;    6-hydroxydopamine;    Dyskinesia;    Transcriptome;    Microarray;    Striatum;   

DOI  :  

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown