title: Reduction of lower motor neuron degeneration in wobbler mice by N-acetyl-L-cysteine.
abstract: The murine mutant wobbler is a model of lower motoneuron degeneration with associated skeletal muscle atrophy. This mutation most closely resembles Werdnig-Hofmann disease in humans and shares some of the clinical features of amyotrophic lateral sclerosis (ALS). It has been suggested that reactive oxygen species (ROS) may play a role in the pathogenesis of disorders such as ALS. To examine the relationship between ROS and neural degeneration, we have studied the effects of agents such as N-acetyl-L-cysteine (NAC), which reduce free radical damage. Litters of wobbler mice were given a 1% solution of the glutathione precursor NAC in their drinking water for a period of 9 weeks. Functional and neuroanatomical examination of these animals revealed that wobbler mice treated with NAC exhibited (1) a significant reduction in motor neuron loss and elevated glutathione peroxidase levels within the cervical spinal cord, (2) increased axon caliber in the medial facial nerve, (3) increased muscle mass and muscle fiber area in the triceps and flexor carpi ulnaris muscles, and (4) increased functional efficiency of the forelimbs, as compared with untreated wobbler littermates. These data suggest that reactive oxygen species may be involved in the degeneration of motor neurons in wobbler mice and demonstrate that oral administration of NAC effectively reduces the degree of motor degeneration in wobbler mice. This treatment thus may be applicable in the treatment of other lower motor neuropathies.
authors.affiliation: Samuel Lunenfeld Research Institute, Program in Development and Fetal Health, Mount Sinai Hospital, Toronto, Ontario, Canada.
authors.forename: J T
authors.initials: JT
authors.lastname: Henderson
authors.forename: M
authors.initials: M
authors.lastname: Javaheri
authors.forename: S
authors.initials: S
authors.lastname: Kopko
authors.forename: J C
authors.initials: JC
authors.lastname: Roder
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D005154:Facial Nerve / Q000187:drug effects / Q000648:ultrastructure; D005552:Forelimb; D016166:Free Radical Scavengers / Q000494:pharmacology*; D005979:Glutathione Peroxidase / Q000378:metabolism; D051379:Mice; D008818:Mice, Neurologic Mutants / Q000502:physiology*; D009046:Motor Neurons / Q000187:drug effects* / Q000502:physiology; D018482:Muscle, Skeletal / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology; D009333:Neck; D009410:Nerve Degeneration / Q000187:drug effects*; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology
chemical_list: D016166:Free Radical Scavengers; D005979:Glutathione Peroxidase; D000111:Acetylcysteine