Mitogen- and stress-activated protein kinase 1 is required for specific signaling responses in dopamine-denervated mouse striatum, but is not necessary for l-DOPA-induced dyskinesia

Research output: Contribution to journalArticle

Abstract

In advanced Parkinson's disease, l-DOPA treatment causes the appearance of abnormal involuntary movements or l-DOPA-induced dyskinesia (LID). LID results in part from l-DOPA-induced activation of extracellular signal-regulated kinase (ERK) in the dopamine-denervated striatum. Activated ERK triggers nuclear responses, including phosphorylation of mitogen- and stress-activated protein kinase 1 (MSK1) and histone H3, and transcription of genes such as FosB. To determine the role of MSK1, wild type and MSK1 knockout mice with unilateral 6-hydroxydopamine lesion in the dorsolateral striatum were chronically treated with l-DOPA. The absence of MSK1 had no effect on the lesion or l-DOPA-induced ERK activation, but reduced l-DOPA-induced phosphorylation of histone H3 and FosB accumulation in the dopamine-denervated striatum. MSK1 deficiency also prevented the increase in Gαolf, the stimulatory α subunit of G protein coupling striatal dopamine D1 receptor to adenylyl cyclase. However, the intensity of LID was similar in MSK1-deficient and wild type mice. In conclusion, l-DOPA-induced activation of MSK1 contributes to histone H3 phosphorylation, induction of FosB, and Gαolf up-regulation but appears not to be necessary for the development of LID.

Details

Authors
  • Cristina Alcacer
  • Fanny Charbonnier-Beaupel
  • Jean-Christophe Corvol
  • Jean-Antoine Girault
  • Denis Hervé
External organisations
  • Pierre and Marie Curie University
Research areas and keywords

Keywords

  • 6-OHDA, Extracellular signal-regulated kinase, L-DOPA-induced dyskinesia, Parkinson's disease, Signaling
Original languageEnglish
Pages (from-to)76-80
Number of pages5
JournalNeuroscience Letters
Volume583
Publication statusPublished - 2014 Nov 7
Publication categoryResearch
Peer-reviewedYes
Externally publishedYes