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Decreased Rhes mRNA levels in the brain of patients with Parkinson’s disease and MPTP-treated macaques

In rodent and human brains, the small GTP-binding protein Rhes is highly expressed in virtually all dopaminoceptive striatal GABAergic medium spiny neurons, as well as in large aspiny cholinergic interneurons, where it is thought to modulate dopamine-dependent signaling. Consistent with this knowled...

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Autores principales: Napolitano, Francesco, Booth Warren, Emily, Migliarini, Sara, Punzo, Daniela, Errico, Francesco, Li, Qin, Thiolat, Marie-Laure, Vescovi, Angelo Luigi, Calabresi, Paolo, Bezard, Erwan, Morelli, Micaela, Konradi, Christine, Pasqualetti, Massimo, Usiello, Alessandro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5526584/
https://www.ncbi.nlm.nih.gov/pubmed/28742811
http://dx.doi.org/10.1371/journal.pone.0181677
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author Napolitano, Francesco
Booth Warren, Emily
Migliarini, Sara
Punzo, Daniela
Errico, Francesco
Li, Qin
Thiolat, Marie-Laure
Vescovi, Angelo Luigi
Calabresi, Paolo
Bezard, Erwan
Morelli, Micaela
Konradi, Christine
Pasqualetti, Massimo
Usiello, Alessandro
author_facet Napolitano, Francesco
Booth Warren, Emily
Migliarini, Sara
Punzo, Daniela
Errico, Francesco
Li, Qin
Thiolat, Marie-Laure
Vescovi, Angelo Luigi
Calabresi, Paolo
Bezard, Erwan
Morelli, Micaela
Konradi, Christine
Pasqualetti, Massimo
Usiello, Alessandro
author_sort Napolitano, Francesco
collection PubMed
description In rodent and human brains, the small GTP-binding protein Rhes is highly expressed in virtually all dopaminoceptive striatal GABAergic medium spiny neurons, as well as in large aspiny cholinergic interneurons, where it is thought to modulate dopamine-dependent signaling. Consistent with this knowledge, and considering that dopaminergic neurotransmission is altered in neurological and psychiatric disorders, here we sought to investigate whether Rhes mRNA expression is altered in brain regions of patients with Parkinson’s disease (PD), Schizophrenia (SCZ), and Bipolar Disorder (BD), when compared to healthy controls (about 200 post-mortem samples). Moreover, we performed the same analysis in the putamen of non-human primate Macaca Mulatta, lesioned with the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Overall, our data indicated comparable Rhes mRNA levels in the brain of patients with SCZ and BD, and their respective healthy controls. In sharp contrast, the putamen of patients suffering from PD showed a significant 35% reduction of this transcript, compared to healthy subjects. Interestingly, in line with observations obtained in humans, we found 27% decrease in Rhes mRNA levels in the putamen of MPTP-treated primates. Based on the established inhibitory influence of Rhes on dopamine-related responses, we hypothesize that its striatal downregulation in PD patients and animal models of PD might represent an adaptive event of the dopaminergic system to functionally counteract the reduced nigrostriatal innervation.
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spelling pubmed-55265842017-08-07 Decreased Rhes mRNA levels in the brain of patients with Parkinson’s disease and MPTP-treated macaques Napolitano, Francesco Booth Warren, Emily Migliarini, Sara Punzo, Daniela Errico, Francesco Li, Qin Thiolat, Marie-Laure Vescovi, Angelo Luigi Calabresi, Paolo Bezard, Erwan Morelli, Micaela Konradi, Christine Pasqualetti, Massimo Usiello, Alessandro PLoS One Research Article In rodent and human brains, the small GTP-binding protein Rhes is highly expressed in virtually all dopaminoceptive striatal GABAergic medium spiny neurons, as well as in large aspiny cholinergic interneurons, where it is thought to modulate dopamine-dependent signaling. Consistent with this knowledge, and considering that dopaminergic neurotransmission is altered in neurological and psychiatric disorders, here we sought to investigate whether Rhes mRNA expression is altered in brain regions of patients with Parkinson’s disease (PD), Schizophrenia (SCZ), and Bipolar Disorder (BD), when compared to healthy controls (about 200 post-mortem samples). Moreover, we performed the same analysis in the putamen of non-human primate Macaca Mulatta, lesioned with the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Overall, our data indicated comparable Rhes mRNA levels in the brain of patients with SCZ and BD, and their respective healthy controls. In sharp contrast, the putamen of patients suffering from PD showed a significant 35% reduction of this transcript, compared to healthy subjects. Interestingly, in line with observations obtained in humans, we found 27% decrease in Rhes mRNA levels in the putamen of MPTP-treated primates. Based on the established inhibitory influence of Rhes on dopamine-related responses, we hypothesize that its striatal downregulation in PD patients and animal models of PD might represent an adaptive event of the dopaminergic system to functionally counteract the reduced nigrostriatal innervation. Public Library of Science 2017-07-25 /pmc/articles/PMC5526584/ /pubmed/28742811 http://dx.doi.org/10.1371/journal.pone.0181677 Text en © 2017 Napolitano et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Napolitano, Francesco
Booth Warren, Emily
Migliarini, Sara
Punzo, Daniela
Errico, Francesco
Li, Qin
Thiolat, Marie-Laure
Vescovi, Angelo Luigi
Calabresi, Paolo
Bezard, Erwan
Morelli, Micaela
Konradi, Christine
Pasqualetti, Massimo
Usiello, Alessandro
Decreased Rhes mRNA levels in the brain of patients with Parkinson’s disease and MPTP-treated macaques
title Decreased Rhes mRNA levels in the brain of patients with Parkinson’s disease and MPTP-treated macaques
title_full Decreased Rhes mRNA levels in the brain of patients with Parkinson’s disease and MPTP-treated macaques
title_fullStr Decreased Rhes mRNA levels in the brain of patients with Parkinson’s disease and MPTP-treated macaques
title_full_unstemmed Decreased Rhes mRNA levels in the brain of patients with Parkinson’s disease and MPTP-treated macaques
title_short Decreased Rhes mRNA levels in the brain of patients with Parkinson’s disease and MPTP-treated macaques
title_sort decreased rhes mrna levels in the brain of patients with parkinson’s disease and mptp-treated macaques
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5526584/
https://www.ncbi.nlm.nih.gov/pubmed/28742811
http://dx.doi.org/10.1371/journal.pone.0181677
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