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NMDA receptor GluN2A/GluN2B subunit ratio as synaptic trait of levodopa-induced dyskinesias: from experimental models to patients
Levodopa-induced dyskinesias (LIDs) are major complications in the pharmacological management of Parkinson’s disease (PD). Abnormal glutamatergic transmission in the striatum is considered a key factor in the development of LIDs. This work aims at: (i) characterizing N-methyl-D-aspartate (NMDA) rece...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4491616/ https://www.ncbi.nlm.nih.gov/pubmed/26217176 http://dx.doi.org/10.3389/fncel.2015.00245 |
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author | Mellone, Manuela Stanic, Jennifer Hernandez, Ledia F. Iglesias, Elena Zianni, Elisa Longhi, Annalisa Prigent, Annick Picconi, Barbara Calabresi, Paolo Hirsch, Etienne C. Obeso, Jose A. Di Luca, Monica Gardoni, Fabrizio |
author_facet | Mellone, Manuela Stanic, Jennifer Hernandez, Ledia F. Iglesias, Elena Zianni, Elisa Longhi, Annalisa Prigent, Annick Picconi, Barbara Calabresi, Paolo Hirsch, Etienne C. Obeso, Jose A. Di Luca, Monica Gardoni, Fabrizio |
author_sort | Mellone, Manuela |
collection | PubMed |
description | Levodopa-induced dyskinesias (LIDs) are major complications in the pharmacological management of Parkinson’s disease (PD). Abnormal glutamatergic transmission in the striatum is considered a key factor in the development of LIDs. This work aims at: (i) characterizing N-methyl-D-aspartate (NMDA) receptor GluN2A/GluN2B subunit ratio as a common synaptic trait in rat and primate models of LIDs as well as in dyskinetic PD patients; and (ii) validating the potential therapeutic effect of a cell-permeable peptide (CPP) interfering with GluN2A synaptic localization on the dyskinetic behavior of these experimental models of LIDs. Here we demonstrate an altered ratio of synaptic GluN2A/GluN2B-containing NMDA receptors in the striatum of levodopa-treated dyskinetic rats and monkeys as well as in post-mortem tissue from dyskinetic PD patients. The modulation of synaptic NMDA receptor composition by a cell-permeable peptide interfering with GluN2A subunit interaction with the scaffolding protein postsynaptic density protein 95 (PSD-95) leads to a reduction in the dyskinetic motor behavior in the two animal models of LIDs. Our results indicate that targeting synaptic NMDA receptor subunit composition may represent an intriguing therapeutic approach aimed at ameliorating levodopa motor side effects. |
format | Online Article Text |
id | pubmed-4491616 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-44916162015-07-27 NMDA receptor GluN2A/GluN2B subunit ratio as synaptic trait of levodopa-induced dyskinesias: from experimental models to patients Mellone, Manuela Stanic, Jennifer Hernandez, Ledia F. Iglesias, Elena Zianni, Elisa Longhi, Annalisa Prigent, Annick Picconi, Barbara Calabresi, Paolo Hirsch, Etienne C. Obeso, Jose A. Di Luca, Monica Gardoni, Fabrizio Front Cell Neurosci Neuroscience Levodopa-induced dyskinesias (LIDs) are major complications in the pharmacological management of Parkinson’s disease (PD). Abnormal glutamatergic transmission in the striatum is considered a key factor in the development of LIDs. This work aims at: (i) characterizing N-methyl-D-aspartate (NMDA) receptor GluN2A/GluN2B subunit ratio as a common synaptic trait in rat and primate models of LIDs as well as in dyskinetic PD patients; and (ii) validating the potential therapeutic effect of a cell-permeable peptide (CPP) interfering with GluN2A synaptic localization on the dyskinetic behavior of these experimental models of LIDs. Here we demonstrate an altered ratio of synaptic GluN2A/GluN2B-containing NMDA receptors in the striatum of levodopa-treated dyskinetic rats and monkeys as well as in post-mortem tissue from dyskinetic PD patients. The modulation of synaptic NMDA receptor composition by a cell-permeable peptide interfering with GluN2A subunit interaction with the scaffolding protein postsynaptic density protein 95 (PSD-95) leads to a reduction in the dyskinetic motor behavior in the two animal models of LIDs. Our results indicate that targeting synaptic NMDA receptor subunit composition may represent an intriguing therapeutic approach aimed at ameliorating levodopa motor side effects. Frontiers Media S.A. 2015-07-06 /pmc/articles/PMC4491616/ /pubmed/26217176 http://dx.doi.org/10.3389/fncel.2015.00245 Text en Copyright © 2015 Mellone, Stanic, Hernandez, Iglesias, Zianni, Longhi, Prigent, Picconi, Calabresi, Hirsch, Obeso, Di Luca and Gardoni. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution and reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Neuroscience Mellone, Manuela Stanic, Jennifer Hernandez, Ledia F. Iglesias, Elena Zianni, Elisa Longhi, Annalisa Prigent, Annick Picconi, Barbara Calabresi, Paolo Hirsch, Etienne C. Obeso, Jose A. Di Luca, Monica Gardoni, Fabrizio NMDA receptor GluN2A/GluN2B subunit ratio as synaptic trait of levodopa-induced dyskinesias: from experimental models to patients |
title | NMDA receptor GluN2A/GluN2B subunit ratio as synaptic trait of levodopa-induced dyskinesias: from experimental models to patients |
title_full | NMDA receptor GluN2A/GluN2B subunit ratio as synaptic trait of levodopa-induced dyskinesias: from experimental models to patients |
title_fullStr | NMDA receptor GluN2A/GluN2B subunit ratio as synaptic trait of levodopa-induced dyskinesias: from experimental models to patients |
title_full_unstemmed | NMDA receptor GluN2A/GluN2B subunit ratio as synaptic trait of levodopa-induced dyskinesias: from experimental models to patients |
title_short | NMDA receptor GluN2A/GluN2B subunit ratio as synaptic trait of levodopa-induced dyskinesias: from experimental models to patients |
title_sort | nmda receptor glun2a/glun2b subunit ratio as synaptic trait of levodopa-induced dyskinesias: from experimental models to patients |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4491616/ https://www.ncbi.nlm.nih.gov/pubmed/26217176 http://dx.doi.org/10.3389/fncel.2015.00245 |
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