Mitochondria exert age-divergent effects on recovery from spinal cord injury.

2,4-Dinitrophenol / pharmacology Aging Animals Cell Survival Disease Progression Female Mice Mice, Inbred C57BL Mitochondria / metabolism Neurodegenerative Diseases / etiology Neurons / pathology Oxidative Stress Oxygen Consumption Reactive Oxygen Species / metabolism Recovery of Function Spinal Cord Injuries / complications Tyrosine / analogs & derivatives Uncoupling Agents / pharmacology
Bioenergetics Metabolism Mitochondrial Uncouplers Mitochondrial oxidative damage Neuroprotection Secondary injury

Journal

Experimental neurology
ISSN: 1090-2430
Titre abrégé: Exp Neurol
Pays: United States
ID NLM: 0370712

Informations de publication

Date de publication:
03 2021
Historique:
received: 07 10 2020
revised: 15 12 2020
accepted: 05 01 2021
pubmed: 11 1 2021
medline: 14 9 2021
entrez: 10 1 2021
Statut: ppublish

Résumé

The extent that age-dependent mitochondrial dysfunction drives neurodegeneration is not well understood. This study tested the hypothesis that mitochondria contribute to spinal cord injury (SCI)-induced neurodegeneration in an age-dependent manner by using 2,4-dinitrophenol (DNP) to uncouple electron transport, thereby increasing cellular respiration and reducing reactive oxygen species (ROS) production. We directly compared the effects of graded DNP doses in 4- and 14-month-old (MO) SCI-mice and found DNP to have increased efficacy in mitochondria isolated from 14-MO animals. In vivo, all DNP doses significantly exacerbated 4-MO SCI neurodegeneration coincident with worsened recovery. In contrast, low DNP doses (1.0-mg/kg/day) improved tissue sparing, reduced ROS-associated 3-nitrotyrosine (3-NT) accumulation, and improved anatomical and functional recovery in 14-MO SCI-mice. By directly comparing the effects of DNP between ages we demonstrate that mitochondrial contributions to neurodegeneration diverge with age after SCI. Collectively, our data indicate an essential role of mitochondria in age-associated neurodegeneration.

Identifiants

DOI: 10.1016/j.expneurol.2021.113597 PMID: 33422552 PMC: PMC7870583
pubmed: 33422552
pii: S0014-4886(21)00002-9
doi: 10.1016/j.expneurol.2021.113597
pmc: PMC7870583
mid: NIHMS1660903
pii:
doi:

Substances chimiques

Reactive Oxygen Species 0
Uncoupling Agents 0
3-nitrotyrosine 3604-79-3
Tyrosine 42HK56048U
2,4-Dinitrophenol Q13SKS21MN

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

113597

Subventions

Organisme : NINDS NIH HHS
ID : F32 NS111241
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS091582
Pays : United States

Informations de copyright

Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.

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Auteurs

Andrew N Stewart (AN)

Department of Physiology, College of Arts and Sciences, University of Kentucky, Lexington, KY 40536, USA; Spinal Cord and Brain Injury Research Center, University of College of Medicine, College of Arts and Sciences, University of Kentucky, Lexington, KY 40536, USA. Electronic address: Andrew.N.Stewart@uky.edu.

Katelyn E McFarlane (KE)

Department of Physiology, College of Arts and Sciences, University of Kentucky, Lexington, KY 40536, USA; Spinal Cord and Brain Injury Research Center, University of College of Medicine, College of Arts and Sciences, University of Kentucky, Lexington, KY 40536, USA.

Hemendra J Vekaria (HJ)

Department of Neuroscience, College of Arts and Sciences, University of Kentucky, Lexington, KY 40536, USA; Spinal Cord and Brain Injury Research Center, University of College of Medicine, College of Arts and Sciences, University of Kentucky, Lexington, KY 40536, USA.

William M Bailey (WM)

Department of Physiology, College of Arts and Sciences, University of Kentucky, Lexington, KY 40536, USA; Spinal Cord and Brain Injury Research Center, University of College of Medicine, College of Arts and Sciences, University of Kentucky, Lexington, KY 40536, USA.

Stacey A Slone (SA)

Department of Statistics, College of Arts and Sciences, University of Kentucky, Lexington, KY 40536, USA.

Lauren A Tranthem (LA)

Department of Physiology, College of Arts and Sciences, University of Kentucky, Lexington, KY 40536, USA; Spinal Cord and Brain Injury Research Center, University of College of Medicine, College of Arts and Sciences, University of Kentucky, Lexington, KY 40536, USA.

Bei Zhang (B)

Brain and Mind Research Institute Weill Cornell, Weill Cornell Medicine, New York, NY, 10021, USA.

Samir P Patel (SP)

Department of Physiology, College of Arts and Sciences, University of Kentucky, Lexington, KY 40536, USA; Spinal Cord and Brain Injury Research Center, University of College of Medicine, College of Arts and Sciences, University of Kentucky, Lexington, KY 40536, USA.

Patrick G Sullivan (PG)

Department of Neuroscience, College of Arts and Sciences, University of Kentucky, Lexington, KY 40536, USA; Spinal Cord and Brain Injury Research Center, University of College of Medicine, College of Arts and Sciences, University of Kentucky, Lexington, KY 40536, USA.

John C Gensel (JC)

Department of Physiology, College of Arts and Sciences, University of Kentucky, Lexington, KY 40536, USA; Spinal Cord and Brain Injury Research Center, University of College of Medicine, College of Arts and Sciences, University of Kentucky, Lexington, KY 40536, USA. Electronic address: gensel.1@uky.edu.

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Classifications MeSH

questionsmedicales.fr › Composés chimiques organiques › Composés nitrés › Nitrophénols › Dinitrophénols › 2,4-Dinitro-phénol › Mitochondria exert age-divergent effects on...
questionsmedicales.fr › Phénomènes physiologiques › Croissance et développement › Vieillissement › Mitochondria exert age-divergent effects on...
questionsmedicales.fr › Eucaryotes › Animaux › Mitochondria exert age-divergent effects on...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Survie cellulaire › Mitochondria exert age-divergent effects on...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Caractéristiques de la maladie › Évolution de la maladie › Mitochondria exert age-divergent effects on...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Mitochondria exert age-divergent effects on...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Lignées consanguines de souris › Souris de lignée C57BL › Mitochondria exert age-divergent effects on...
questionsmedicales.fr › Cellules › Structures cellulaires › Fractions subcellulaires › Mitochondries › Mitochondria exert age-divergent effects on...
questionsmedicales.fr › Maladies du système nerveux › Maladies neurodégénératives › Mitochondria exert age-divergent effects on...
questionsmedicales.fr › Cellules › Neurones › Mitochondria exert age-divergent effects on...
questionsmedicales.fr › Phénomènes physiologiques › Stress physiologique › Stress oxydatif › Mitochondria exert age-divergent effects on...
questionsmedicales.fr › Métabolisme › Consommation d'oxygène › Mitochondria exert age-divergent effects on...
questionsmedicales.fr › Produits chimiques inorganiques › Composés de l'oxygène › Espèces réactives de l'oxygène › Mitochondria exert age-divergent effects on...
questionsmedicales.fr › Phénomènes biologiques › Récupération fonctionnelle › Mitochondria exert age-divergent effects on...
questionsmedicales.fr › Plaies et blessures › Traumatismes de la moelle épinière › Mitochondria exert age-divergent effects on...
questionsmedicales.fr › Acides aminés, peptides et protéines › Acides aminés › Acides aminés cycliques › Acides aminés aromatiques › Tyrosine › Mitochondria exert age-divergent effects on...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Mécanismes moléculaires de l'action pharmacologique › Antienzymes › Agents découplants › Mitochondria exert age-divergent effects on...