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

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

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.

Detaljer

Författare
  • Cristina Alcacer
  • Fanny Charbonnier-Beaupel
  • Jean-Christophe Corvol
  • Jean-Antoine Girault
  • Denis Hervé
Externa organisationer
  • Pierre and Marie Curie University
Forskningsområden

Nyckelord

Originalspråkengelska
Sidor (från-till)76-80
Antal sidor5
TidskriftNeuroscience Letters
Volym583
StatusPublished - 2014 nov 7
PublikationskategoriForskning
Peer review utfördJa
Externt publiceradJa