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




Distinct changes in cAMP and extracellular signal-regulated protein kinase signalling in L-DOPA-induced dyskinesia. - Download this document for free, or read online. Document in PDF available to download.

* Corresponding author 1 Departement Neurosciences 2 CNC - Centre de neuroscience cognitive 3 Institute of Lab Animal Sciences 4 MAC - Laboratoire Mouvement Adaptation Cognition 5 INSERM U836, équipe 10, Dynamique des réseaux neuronaux du mouvement GIN - Grenoble Institut des Neurosciences

Abstract : BACKGROUND: 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. METHODOLOGY-RESULTS: 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. CONCLUSION: 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.





Author: Emanuela Santini - Veronique Sgambato-Faure - Qin Li - Marc Savasta - Sandra Dovero - Gilberto Fisone - Erwan Bezard -

Source: https://hal.archives-ouvertes.fr/



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