Mitochondria Exert Age-divergent Effects on Recovery from Spinal Cord Injury

Overview

Journal Exp Neurol

Specialty Neurology

Date 2021 Jan 10

PMID 33422552

Citations 10

Authors

Andrew N Stewart

Katelyn E McFarlane

Hemendra J Vekaria

William M Bailey

Stacey A Slone

Lauren A Tranthem

Bei Zhang

Samir P Patel

Patrick G Sullivan

John C Gensel

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Challenges in Translating Regenerative Therapies for Spinal Cord Injury.

Stewart A, Gensel J, Jones L, Fouad K Top Spinal Cord Inj Rehabil. 2024; 29(Suppl):23-43.

PMID: 38174141 PMC: 10759906. DOI: 10.46292/sci23-00044S.

Prognostic Value of Malondialdehyde (MDA) in the Temporal Progression of Chronic Spinal Cord Injury.

Giron S, Monserrat Sanz J, Ortega M, Garcia-Montero C, Fraile-Martinez O, Gomez-Lahoz A J Pers Med. 2023; 13(4).

PMID: 37109013 PMC: 10144495. DOI: 10.3390/jpm13040626.

Data and subject heterogeneity and data sharing: keys to translational success in spinal cord injury research?.

Fouad K, Wireman O, Gensel J Neural Regen Res. 2023; 18(8):1730-1731.

PMID: 36751797 PMC: 10154489. DOI: 10.4103/1673-5374.363191.

Improving translatability of spinal cord injury research by including age as a demographic variable.

Stewart A, Jones L, Gensel J Front Cell Neurosci. 2022; 16:1017153.

PMID: 36467608 PMC: 9714671. DOI: 10.3389/fncel.2022.1017153.

Melatonin Attenuates Spinal Cord Injury in Mice by Activating the Nrf2/ARE Signaling Pathway to Inhibit the NLRP3 Inflammasome.

Wang H, Wang H, Huang H, Qu Z, Ma D, Dang X Cells. 2022; 11(18).

PMID: 36139384 PMC: 9496911. DOI: 10.3390/cells11182809.

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