TY - JOUR T1 - Reduction of Lower Motor Neuron Degeneration in<em>wobbler</em> Mice by<em>N</em>-Acetyl-<span class="sc">l</span>-Cysteine JF - The Journal of Neuroscience JO - J. Neurosci. SP - 7574 LP - 7582 DO - 10.1523/JNEUROSCI.16-23-07574.1996 VL - 16 IS - 23 AU - Jeffrey T. Henderson AU - Mohammed Javaheri AU - Susan Kopko AU - John C. Roder Y1 - 1996/12/01 UR - http://www.jneurosci.org/content/16/23/7574.abstract N2 - 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 asN-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. ER -