Gene Expression Analyses Identify Narp Contribution in the Development of l-DOPA-Induced Dyskinesia

• DOI: 10.1523/jneurosci.5231-13.2015
• Publication Date: 2015-01-08T01:14:10Z
• Authors: Fanny Charbonnier...; Marion Malerbi; Cristina Alcacer; Khadija Tahiri; Wassila Carpentier; Chuansong Wang; Matthew During; Desheng Xu; Paul F. Worley; Jean-Antoine Girault; Denis Hervé; Jean-Christophe C...
• Keywords: FOSB

In Parkinson's disease, long-term dopamine replacement therapy is complicated by the appearance of l -DOPA-induced dyskinesia (LID). One major hypothesis that LID results from an aberrant transcriptional program in striatal neurons induced -DOPA and triggered activation ERK. To identify these genes, we performed transcriptome analyses striatum 6-hydroxydopamine-lesioned mice. A time course analysis (0–6 h after treatment with -DOPA) identified acute signature 709 among which genes involved protein phosphatase activity were overrepresented, suggesting a negative feedback on ERK -DOPA. -DOPA-dependent deregulation 28 was blocked pretreatment SL327, inhibitor activation, 26 found differentially expressed between highly weakly dyskinetic animals The intersection list five genes: FosB , Th Nptx2 Nedd4l Ccrn4l. encodes neuronal pentraxin II (or activity-regulated pentraxin, Narp), clustering glutamate receptors. We confirmed increased expression its blockade SL327 using quantitative RT-PCR independent experiments. Using escalating dose protocol, severity decreased Narp knock-out mice compared their wild-type littermates or overexpression dominant-negative form striatum. conclusion, have molecular dopamine-denervated dependent associated LID. Here, demonstrate implication one development