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Mitochondrial impairment and melatonin protection in parkinsonian mice do not depend of inducible or neuronal nitric oxide synthases

MPTP-mouse model constitutes a well-known model of neuroinflammation and mitochondrial failure occurring in Parkinson’s disease (PD). Although it has been extensively reported that nitric oxide (NO(●)) plays a key role in the pathogenesis of PD, the relative roles of nitric oxide synthase isoforms i...

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Autores principales: López, Ana, Ortiz, Francisco, Doerrier, Carolina, Venegas, Carmen, Fernández-Ortiz, Marisol, Aranda, Paula, Díaz-Casado, María E., Fernández-Gil, Beatriz, Barriocanal-Casado, Eliana, Escames, Germaine, López, Luis C., Acuña-Castroviejo, Darío
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5553810/
https://www.ncbi.nlm.nih.gov/pubmed/28800639
http://dx.doi.org/10.1371/journal.pone.0183090
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author López, Ana
Ortiz, Francisco
Doerrier, Carolina
Venegas, Carmen
Fernández-Ortiz, Marisol
Aranda, Paula
Díaz-Casado, María E.
Fernández-Gil, Beatriz
Barriocanal-Casado, Eliana
Escames, Germaine
López, Luis C.
Acuña-Castroviejo, Darío
author_facet López, Ana
Ortiz, Francisco
Doerrier, Carolina
Venegas, Carmen
Fernández-Ortiz, Marisol
Aranda, Paula
Díaz-Casado, María E.
Fernández-Gil, Beatriz
Barriocanal-Casado, Eliana
Escames, Germaine
López, Luis C.
Acuña-Castroviejo, Darío
author_sort López, Ana
collection PubMed
description MPTP-mouse model constitutes a well-known model of neuroinflammation and mitochondrial failure occurring in Parkinson’s disease (PD). Although it has been extensively reported that nitric oxide (NO(●)) plays a key role in the pathogenesis of PD, the relative roles of nitric oxide synthase isoforms iNOS and nNOS in the nigrostriatal pathway remains, however, unclear. Here, the participation of iNOS/nNOS isoforms in the mitochondrial dysfunction was analyzed in iNOS and nNOS deficient mice. Our results showed that MPTP increased iNOS activity in substantia nigra and striatum, whereas it sharply reduced complex I activity and mitochondrial bioenergetics in all strains. In the presence of MPTP, mice lacking iNOS showed similar restricted mitochondrial function than wild type or mice lacking nNOS. These results suggest that iNOS-dependent elevated nitric oxide, a major pathological hallmark of neuroinflammation in PD, does not contribute to mitochondrial impairment. Therefore, neuroinflammation and mitochondrial dysregulation seem to act in parallel in the MPTP model of PD. Melatonin administration, with well-reported neuroprotective properties, counteracted these effects, preventing from the drastic changes in mitochondrial oxygen consumption, increased NOS activity and prevented reduced locomotor activity induced by MPTP. The protective effects of melatonin on mitochondria are also independent of its anti-inflammatory properties, but both effects are required for an effective anti-parkinsonian activity of the indoleamine as reported in this study.
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spelling pubmed-55538102017-08-25 Mitochondrial impairment and melatonin protection in parkinsonian mice do not depend of inducible or neuronal nitric oxide synthases López, Ana Ortiz, Francisco Doerrier, Carolina Venegas, Carmen Fernández-Ortiz, Marisol Aranda, Paula Díaz-Casado, María E. Fernández-Gil, Beatriz Barriocanal-Casado, Eliana Escames, Germaine López, Luis C. Acuña-Castroviejo, Darío PLoS One Research Article MPTP-mouse model constitutes a well-known model of neuroinflammation and mitochondrial failure occurring in Parkinson’s disease (PD). Although it has been extensively reported that nitric oxide (NO(●)) plays a key role in the pathogenesis of PD, the relative roles of nitric oxide synthase isoforms iNOS and nNOS in the nigrostriatal pathway remains, however, unclear. Here, the participation of iNOS/nNOS isoforms in the mitochondrial dysfunction was analyzed in iNOS and nNOS deficient mice. Our results showed that MPTP increased iNOS activity in substantia nigra and striatum, whereas it sharply reduced complex I activity and mitochondrial bioenergetics in all strains. In the presence of MPTP, mice lacking iNOS showed similar restricted mitochondrial function than wild type or mice lacking nNOS. These results suggest that iNOS-dependent elevated nitric oxide, a major pathological hallmark of neuroinflammation in PD, does not contribute to mitochondrial impairment. Therefore, neuroinflammation and mitochondrial dysregulation seem to act in parallel in the MPTP model of PD. Melatonin administration, with well-reported neuroprotective properties, counteracted these effects, preventing from the drastic changes in mitochondrial oxygen consumption, increased NOS activity and prevented reduced locomotor activity induced by MPTP. The protective effects of melatonin on mitochondria are also independent of its anti-inflammatory properties, but both effects are required for an effective anti-parkinsonian activity of the indoleamine as reported in this study. Public Library of Science 2017-08-11 /pmc/articles/PMC5553810/ /pubmed/28800639 http://dx.doi.org/10.1371/journal.pone.0183090 Text en © 2017 López 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
López, Ana
Ortiz, Francisco
Doerrier, Carolina
Venegas, Carmen
Fernández-Ortiz, Marisol
Aranda, Paula
Díaz-Casado, María E.
Fernández-Gil, Beatriz
Barriocanal-Casado, Eliana
Escames, Germaine
López, Luis C.
Acuña-Castroviejo, Darío
Mitochondrial impairment and melatonin protection in parkinsonian mice do not depend of inducible or neuronal nitric oxide synthases
title Mitochondrial impairment and melatonin protection in parkinsonian mice do not depend of inducible or neuronal nitric oxide synthases
title_full Mitochondrial impairment and melatonin protection in parkinsonian mice do not depend of inducible or neuronal nitric oxide synthases
title_fullStr Mitochondrial impairment and melatonin protection in parkinsonian mice do not depend of inducible or neuronal nitric oxide synthases
title_full_unstemmed Mitochondrial impairment and melatonin protection in parkinsonian mice do not depend of inducible or neuronal nitric oxide synthases
title_short Mitochondrial impairment and melatonin protection in parkinsonian mice do not depend of inducible or neuronal nitric oxide synthases
title_sort mitochondrial impairment and melatonin protection in parkinsonian mice do not depend of inducible or neuronal nitric oxide synthases
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5553810/
https://www.ncbi.nlm.nih.gov/pubmed/28800639
http://dx.doi.org/10.1371/journal.pone.0183090
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