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

被引:16
|
作者
Stommel, E. W.
Van Hoff, R. M.
Graber, D. J.
Bercury, K. K.
Langford, G. M.
Harris, B. T.
机构
[1] Dartmouth Coll, Hitchcock Med Ctr, Neurol Sect, Dept Med, Lebanon, NH 03756 USA
[2] Dartmouth Coll, Hitchcock Med Ctr, Dept Pathol, Lebanon, NH 03756 USA
[3] Dartmouth Coll, Dept Biol, Hanover, NH 03755 USA
关键词
amyotrophic lateral sclerosis; mitochondria; motor neurons; axonal transport; tumor necrosis factor-alpha;
D O I
10.1016/j.neuroscience.2007.02.036
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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. (c) 2007 IBRO. Published by Elsevier Ltd. All rights reserved.
引用
收藏
页码:1013 / 1019
页数:7
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