Please use this identifier to cite or link to this item:
Title: Mitochondrial impairment and melatonin protection in parkinsonian mice do not depend of inducible or neuronal nitric oxide synthases.
Authors: 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
metadata.dc.subject.mesh: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Corpus Striatum
Gene Expression Regulation
Mice, Inbred C57BL
Mice, Knockout
Neuroprotective Agents
Nitric Oxide
Nitric Oxide Synthase Type I
Nitric Oxide Synthase Type II
Oxygen Consumption
Parkinson Disease, Secondary
Substantia Nigra
Issue Date: 11-Aug-2017
Abstract: 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.
metadata.dc.identifier.doi: 10.1371/journal.pone.0183090
Appears in Collections:Producción 2020

Files in This Item:
File SizeFormat 
PMC5553810.pdf10,66 MBAdobe PDFView/Open

This item is protected by original copyright

This item is licensed under a Creative Commons License Creative Commons