Effect of mitochondrial transcription factor a overexpression on motor neurons in amyotrophic lateral sclerosis model mice

Nobutoshi Morimoto, Kazunori Miyazaki, Tomoko Kurata, Yoshio Ikeda, Tohru Matsuura, Dongchon Kang, Tomomi Ide, Koji Abe

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Increasing evidence indicates that oxidative stress is an important mechanism underlying motor neuron (MN) degeneration in amyotrophic lateral sclerosis (ALS). Mitochondrial DNA (mtDNA) is highly susceptible to oxidative damage and has little potential for repair, although mitochondrial transcription factor A (TFAM) plays essential roles in maintaining mitochondrial DNA by reducing oxidative stress, promoting mtDNA transcription, and regulating mtDNA copy number. To analyze a possible therapeutic effect of TFAM on ALS pathology, double transgenic mice overexpressing G93A mutant SOD1 (G93ASOD1) and human TFAM (hTFAM) were newly generated in the present study. Rotarod scores were better in G93ASOD1/hTFAM double-Tg mice than G93ASOD1 single-Tg mice at an early symptomatic stage, 15 and 16 weeks of age, with a 10% extension of the onset age in double-Tg mice. The number of surviving MNs was 30% greater in double-Tg mice with end-stage disease, at 19 weeks, with remarkable reductions in the amount of the oxidative stress marker 8-OHdG and the apoptotic marker cleaved caspase 3 and with preserved COX1 expression. Double-immunofluorescence study showed that hTFAM was expressed specifically in MNs and microglia in the spinal cords of double-Tg mice. The present study suggests that overexpression of TFAM has a potential to reduce oxidative stress in MN and delay onset of the disease in ALS model mice.

Original languageEnglish
Pages (from-to)1200-1208
Number of pages9
JournalJournal of Neuroscience Research
Volume90
Issue number6
DOIs
Publication statusPublished - Jun 1 2012

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Amyotrophic Lateral Sclerosis
Motor Neurons
Transcription Factors
Mitochondrial DNA
Oxidative Stress
Nerve Degeneration
Microglia
Therapeutic Uses
Age of Onset
Caspase 3
Transgenic Mice
Fluorescent Antibody Technique
Spinal Cord
Pathology

All Science Journal Classification (ASJC) codes

  • Cellular and Molecular Neuroscience

Cite this

Effect of mitochondrial transcription factor a overexpression on motor neurons in amyotrophic lateral sclerosis model mice. / Morimoto, Nobutoshi; Miyazaki, Kazunori; Kurata, Tomoko; Ikeda, Yoshio; Matsuura, Tohru; Kang, Dongchon; Ide, Tomomi; Abe, Koji.

In: Journal of Neuroscience Research, Vol. 90, No. 6, 01.06.2012, p. 1200-1208.

Research output: Contribution to journalArticle

Morimoto, Nobutoshi ; Miyazaki, Kazunori ; Kurata, Tomoko ; Ikeda, Yoshio ; Matsuura, Tohru ; Kang, Dongchon ; Ide, Tomomi ; Abe, Koji. / Effect of mitochondrial transcription factor a overexpression on motor neurons in amyotrophic lateral sclerosis model mice. In: Journal of Neuroscience Research. 2012 ; Vol. 90, No. 6. pp. 1200-1208.
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