Tumor necrosis factor-alpha induces changes in mitochondrial cellular distribution in motor neurons

E. W. Stommel, R. M. van Hoff, D. J. Graber, K. K. Bercury, George M Langford, B. T. Harris

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Motor neuron (MN) mitochondrial abnormalities and elevation in spinal fluid levels of the inflammatory cytokine tumor necrosis factor-alpha (TNF-α) have been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS). The mechanism of neuron death in ALS remains unclear, along with the contributions of mitochondrial dysfunction and inflammation in the process. Cell cultures enriched for MN derived from embryonic rat spinal cords were established and directly exposed in vitro to recombinant TNF-α for varying lengths of time. Although cytokine exposure for up to 4 days failed to induce MN death, mitochondrial changes were observed shortly after initiating treatment. Our results demonstrate that TNF-α induced mitochondrial redistribution toward the soma in MN. We postulate that inflammation may precede, and in fact cause, the mitochondrial changes observed in ALS tissue.

Original languageEnglish (US)
Pages (from-to)1013-1019
Number of pages7
JournalNeuroscience
Volume146
Issue number3
DOIs
StatePublished - May 25 2007
Externally publishedYes

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Keywords

  • amyotrophic lateral sclerosis
  • axonal transport
  • mitochondria
  • motor neurons
  • tumor necrosis factor-alpha

ASJC Scopus subject areas

  • Neuroscience(all)

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