Distinct changes in cAMP and extracellular signal-regulated protein kinase signalling in L-DOPA-induced dyskinesia.

<h4>Background</h4>In rodents, the development of dyskinesia produced by L-DOPA in the dopamine-depleted striatum occurs in response to increased dopamine D1 receptor-mediated activation of the cAMP - protein kinase A and of the Ras-extracellular signal-regulated kinase (ERK) signalling...

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Autores principales:	Emanuela Santini, Veronique Sgambato-Faure, Qin Li, Marc Savasta, Sandra Dovero, Gilberto Fisone, Erwan Bezard
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f1d6fedef81d4d898a7f2cf72f1af488
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spelling	oai:doaj.org-article:f1d6fedef81d4d898a7f2cf72f1af4882021-11-18T06:35:48ZDistinct changes in cAMP and extracellular signal-regulated protein kinase signalling in L-DOPA-induced dyskinesia.1932-620310.1371/journal.pone.0012322https://doaj.org/article/f1d6fedef81d4d898a7f2cf72f1af4882010-08-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20808799/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>In rodents, the development of dyskinesia produced by L-DOPA in the dopamine-depleted striatum occurs in response to increased dopamine D1 receptor-mediated activation of the cAMP - protein kinase A and of the Ras-extracellular signal-regulated kinase (ERK) signalling pathways. However, very little is known, in non-human primates, about the regulation of these signalling cascades and their association with the induction, manifestation and/or maintenance of dyskinesia.<h4>Methodology/results</h4>We here studied, in the gold-standard non-human primate model of Parkinson's disease, the changes in PKA-dependent phosphorylation of DARPP-32 and GluR1 AMPA receptor, as well as in ERK and ribosomal protein S6 (S6) phosphorylation, associated to acute and chronic administration of L-DOPA. Increased phosphorylation of DARPP-32 and GluR1 was observed in both L-DOPA first-ever exposed and chronically-treated dyskinetic parkinsonian monkeys. In contrast, phosphorylation of ERK and S6 was enhanced preferentially after acute L-DOPA administration and decreased during the course of chronic treatment.<h4>Conclusion</h4>Dysregulation of cAMP signalling is maintained during the course of chronic L-DOPA administration, while abnormal ERK signalling peaks during the initial phase of L-DOPA treatment and decreases following prolonged exposure. While cAMP signalling enhancement is associated with dyskinesia, abnormal ERK signalling is associated with priming.Emanuela SantiniVeronique Sgambato-FaureQin LiMarc SavastaSandra DoveroGilberto FisoneErwan BezardPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 8, p e12322 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Emanuela Santini Veronique Sgambato-Faure Qin Li Marc Savasta Sandra Dovero Gilberto Fisone Erwan Bezard Distinct changes in cAMP and extracellular signal-regulated protein kinase signalling in L-DOPA-induced dyskinesia.
description	<h4>Background</h4>In rodents, the development of dyskinesia produced by L-DOPA in the dopamine-depleted striatum occurs in response to increased dopamine D1 receptor-mediated activation of the cAMP - protein kinase A and of the Ras-extracellular signal-regulated kinase (ERK) signalling pathways. However, very little is known, in non-human primates, about the regulation of these signalling cascades and their association with the induction, manifestation and/or maintenance of dyskinesia.<h4>Methodology/results</h4>We here studied, in the gold-standard non-human primate model of Parkinson's disease, the changes in PKA-dependent phosphorylation of DARPP-32 and GluR1 AMPA receptor, as well as in ERK and ribosomal protein S6 (S6) phosphorylation, associated to acute and chronic administration of L-DOPA. Increased phosphorylation of DARPP-32 and GluR1 was observed in both L-DOPA first-ever exposed and chronically-treated dyskinetic parkinsonian monkeys. In contrast, phosphorylation of ERK and S6 was enhanced preferentially after acute L-DOPA administration and decreased during the course of chronic treatment.<h4>Conclusion</h4>Dysregulation of cAMP signalling is maintained during the course of chronic L-DOPA administration, while abnormal ERK signalling peaks during the initial phase of L-DOPA treatment and decreases following prolonged exposure. While cAMP signalling enhancement is associated with dyskinesia, abnormal ERK signalling is associated with priming.
format	article
author	Emanuela Santini Veronique Sgambato-Faure Qin Li Marc Savasta Sandra Dovero Gilberto Fisone Erwan Bezard
author_facet	Emanuela Santini Veronique Sgambato-Faure Qin Li Marc Savasta Sandra Dovero Gilberto Fisone Erwan Bezard
author_sort	Emanuela Santini
title	Distinct changes in cAMP and extracellular signal-regulated protein kinase signalling in L-DOPA-induced dyskinesia.
title_short	Distinct changes in cAMP and extracellular signal-regulated protein kinase signalling in L-DOPA-induced dyskinesia.
title_full	Distinct changes in cAMP and extracellular signal-regulated protein kinase signalling in L-DOPA-induced dyskinesia.
title_fullStr	Distinct changes in cAMP and extracellular signal-regulated protein kinase signalling in L-DOPA-induced dyskinesia.
title_full_unstemmed	Distinct changes in cAMP and extracellular signal-regulated protein kinase signalling in L-DOPA-induced dyskinesia.
title_sort	distinct changes in camp and extracellular signal-regulated protein kinase signalling in l-dopa-induced dyskinesia.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/f1d6fedef81d4d898a7f2cf72f1af488
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Distinct changes in cAMP and extracellular signal-regulated protein kinase signalling in L-DOPA-induced dyskinesia.

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