Tumor necrosis factor-alpha induces changes in mitochondrial cellular distribution in motor neurons.
Motor neuron (MN) mitochondrial abnormalities and elevation in spinal fluid levels of the inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) 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-alpha 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-alpha 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.
Stommel
E W
EW
Department of Medicine, Section of Neurology, Dartmouth-Hitchcock Medical Center, One Medical Center Drive, Lebanon, NH 03756, and Department of Biology, Dartmouth College, Hanover 03755, USA. elijah.w.stommel@hitchcock.org
van Hoff
R M
RM
Graber
D J
DJ
Bercury
K K
KK
Langford
G M
GM
Harris
B T
BT
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D066298:In Vitro Techniques; D018715:Microscopy, Video; D008928:Mitochondria / Q000187:drug effects* / Q000648:ultrastructure; D009046:Motor Neurons / Q000187:drug effects* / Q000648:ultrastructure; D009336:Necrosis; D051381:Rats; D017207:Rats, Sprague-Dawley; D016707:Tissue Fixation; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D014409:Tumor Necrosis Factor-alpha