title: 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.
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.
authors.affiliation: Inserm UMR-S 839, Paris, France; Université Pierre et Marie Curie (UPMC), Sorbonne Universités, Paris, France; Institut du Fer à Moulin, Paris, France.
authors.forename: Cristina
authors.initials: C
authors.lastname: Alcacer
authors.affiliation: Université Pierre et Marie Curie (UPMC), Sorbonne Universités, Paris, France; Inserm, UMR-S 1027, Institut du Cerveau et de la Moelle épinière, Pitié-Salpêtrière Hospital, Paris, France; CNRS, UMR 7225, Paris, France; Assistance Publique Hôpitaux de Paris, Department of Pharmacy, Pitié-Salpêtrière Hospital, France.
authors.forename: Fanny
authors.initials: F
authors.lastname: Charbonnier-Beaupel
authors.affiliation: Université Pierre et Marie Curie (UPMC), Sorbonne Universités, Paris, France; Inserm, UMR-S 1027, Institut du Cerveau et de la Moelle épinière, Pitié-Salpêtrière Hospital, Paris, France; CNRS, UMR 7225, Paris, France; Assistance Publique Hôpitaux de Paris, Inserm, Clinical Investigation Center (CIC-1422), Department of Neurology, Pitié-Salpêtrière Hospital, Paris, France.
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Corvol
authors.affiliation: Inserm UMR-S 839, Paris, France; Université Pierre et Marie Curie (UPMC), Sorbonne Universités, Paris, France; Institut du Fer à Moulin, Paris, France.
authors.forename: Jean-Antoine
authors.initials: JA
authors.lastname: Girault
authors.affiliation: Inserm UMR-S 839, Paris, France; Université Pierre et Marie Curie (UPMC), Sorbonne Universités, Paris, France; Institut du Fer à Moulin, Paris, France. Electronic address: denis.herve@inserm.fr.
authors.forename: Denis
authors.initials: D
authors.lastname: Hervé
mesh_terms: D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology*; D003342:Corpus Striatum / Q000378:metabolism* / Q000473:pathology; D004295:Dihydroxyphenylalanine / Q000009:adverse effects*; D059290:Dopaminergic Neurons / Q000473:pathology*; D004409:Dyskinesia, Drug-Induced / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D005260:Female; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009154:Mutation; D016627:Oxidopamine; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D000978:Antiparkinson Agents; D004295:Dihydroxyphenylalanine; D016627:Oxidopamine; D038744:Ribosomal Protein S6 Kinases, 90-kDa; C116919:mitogen and stress-activated protein kinase 1
keywords: 6-OHDA; Extracellular signal-regulated kinase; L-DOPA-induced dyskinesia; Parkinson's disease; Signaling