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.
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New York Med Coll, Dept Pharmacol, Valhalla, NY 10595 USANew York Med Coll, Dept Pharmacol, Valhalla, NY 10595 USA
Ferreri, Nicholas R.
Hao, Shoujin
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New York Med Coll, Dept Pharmacol, Valhalla, NY 10595 USANew York Med Coll, Dept Pharmacol, Valhalla, NY 10595 USA
Hao, Shoujin
Pedraza, Paulina L.
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New York Med Coll, Dept Pharmacol, Valhalla, NY 10595 USANew York Med Coll, Dept Pharmacol, Valhalla, NY 10595 USA
Pedraza, Paulina L.
Escalante, Bruno
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CINVESTAV, Dept Mol Biomed, Ctr Adv Res & Study, Natl Polytech Inst, Mexico City 14000, DF, MexicoNew York Med Coll, Dept Pharmacol, Valhalla, NY 10595 USA
Escalante, Bruno
Vio, Carlos P.
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Pontificia Univ Catolica Chile, Dept Physiol, Ctr Aging & Regenerat, CARE UC, Santiago, ChileNew York Med Coll, Dept Pharmacol, Valhalla, NY 10595 USA
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Pusan Natl Univ, Dept Pharmacol, Sch Med, Yangsan 626870, South KoreaPusan Natl Univ, Dept Pharmacol, Sch Med, Yangsan 626870, South Korea
Kim, Sun-Mi
Jang, Hyojung
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Pusan Natl Univ, Dept Pharmacol, Sch Med, Yangsan 626870, South KoreaPusan Natl Univ, Dept Pharmacol, Sch Med, Yangsan 626870, South Korea
Jang, Hyojung
Son, Yonghae
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Pusan Natl Univ, Dept Pharmacol, Sch Med, Yangsan 626870, South KoreaPusan Natl Univ, Dept Pharmacol, Sch Med, Yangsan 626870, South Korea
Son, Yonghae
Lee, Sae-A.
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Pusan Natl Univ, Dept Pharmacol, Sch Med, Yangsan 626870, South KoreaPusan Natl Univ, Dept Pharmacol, Sch Med, Yangsan 626870, South Korea
Lee, Sae-A.
Bae, Sun-Sik
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Pusan Natl Univ, Dept Pharmacol, Sch Med, Yangsan 626870, South KoreaPusan Natl Univ, Dept Pharmacol, Sch Med, Yangsan 626870, South Korea
Bae, Sun-Sik
Park, Young Chul
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Pusan Natl Univ, Sch Med, Dept Microbiol & Immunol, Yangsan 626870, South KoreaPusan Natl Univ, Dept Pharmacol, Sch Med, Yangsan 626870, South Korea
Park, Young Chul
Eo, Seong-Kug
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Chonbuk Natl Univ, Microbiol Lab, Coll Vet Med, Jeonju 561756, South Korea
Chonbuk Natl Univ, Biosafety Res Inst, Jeonju 561756, South KoreaPusan Natl Univ, Dept Pharmacol, Sch Med, Yangsan 626870, South Korea