Peripheral axotomy slows motoneuron degeneration in a transgenic mouse line expressing mutant SOD1 G93A.
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder that involves motoneuron degeneration, paralysis, and death. Mutations in Cu, Zn superoxide dismutase (SOD1) are one cause of this disease. It has been a puzzle as to why mutations in SOD1, an enzyme expressed in many neuronal types, selectively kill motoneurons. To begin to explore the factors that determine this selectivity, we carried out peripheral axotomy in mice expressing a mutant SOD1 (G93A mice) and controls (nontransgenic mice and mice expressing wild-type human SOD1). Axotomy in controls induced a predicted axonal atrophy and a small degree of axon loss. The axonal atrophy led to an increase in the number of small axons and a decrease in the number of large axons. In contrast to the controls, axotomy in G93A mice reduced the extent of axon degeneration at the end stage of the disease, leading to an increase in the number of surviving motor axons. Interestingly, all of the increased surviving axons were in the axon group with diameters smaller than 4.5 microm. This result suggests an apparent threshold of vulnerability that is correlated with axon size.
Kong
J
J
Department of Pharmacology and Molecular Toxicology, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA.
Xu
Z
Z
D019943:Amino Acid Substitution; D000690:Amyotrophic Lateral Sclerosis / Q000201:enzymology / Q000235:genetics; D000818:Animals; D019771:Axotomy; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000473:pathology*; D009410:Nerve Degeneration / Q000473:pathology / Q000503:physiopathology* / Q000517:prevention & control; D017354:Point Mutation; D013116:Spinal Cord / Q000473:pathology; D013126:Spinal Nerve Roots / Q000473:pathology*; D013482:Superoxide Dismutase / Q000235:genetics* / Q000378:metabolism*
D013482:Superoxide Dismutase