[Proximal axonal injuries as experimental models for adult motoneuron degeneration]

Abstract

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder characterized by selective loss of motoneurons leading to progressive paralysis and death by respiratory failure. Since the discovery of the mutation of Cu/Zn superoxide dismutase (SOD1) gene in patients with familial ALS, transgenic mice and rats expressing human mutant SOD1 have been the most widely used experimental models to elucidate the pathomechanism of and the therapeutic approach against familial ALS as well as sporadic ALS. Most cases of ALS, however, are considered to be sporadic and of unknown etiology. In another animal model of adult motoneuron degeneration, proximal axonal injury (avulsion) of peripheral nerves exhibits extensive loss of motoneurons in adult rats. The mechanism of motoneuron degeneration after avulsion also remains unclear, but peroxinitrite-mediated oxidative damage and perikaryal accumulation of phosphorylated neurofilaments have been demonstrated in injured motoneurons after avulsion. Both of these pathological features have also been shown in spinal motoneurons in mutant SOD1-tg animals as well as in patients with familial and sporadic ALS. In this review, we presented experimental studies on peripheral nerve avulsion models in adult rats to investigate pathomechanisms of motoneuron degeneration and to explore therapeutic strategies against motoneuron injury and motoneuron diseases such as ALS.