title: Neuromuscular dysfunction in the mutant superoxide dismutase mouse model of amyotrophic lateral sclerosis.
abstract: To better understand the interaction between motor neuron dysfunction and denervation in amyotrophic lateral sclerosis (ALS), we have evaluated motor neuron number and the retrograde uptake and transport of fluorogold by motor neurons in mice overexpressing mutant superoxide dismutase (mSOD), and wild-type controls. N-CAM immunoreactivity and protein kinase expression were determined in skeletal muscle during denervation. We found that in severely affected mSOD mice, motor neuron loss is moderate (approximate 40% reduction), whereas retrograde uptake/transport as assessed using fluorogold is profoundly impaired (approximately 90% reduction). The impairment in fluorogold uptake/transport corresponds to measures of progressive muscle denervation such as increased N-CAM immunoreactivity of muscle and increased expression of protein kinase B (PKB) in denervated muscle. These data suggest that the debility in the mSOD mouse model of ALS is produced, in part, by impaired retrograde uptake/transport in motor neuron axons in spite of regenerative support from muscle such as elevated expression of PKB.
authors.affiliation: Metabolic Biochemistry Laboratory, School of Kinesiology, Simon Fraser University, Burnaby, BC, Canada. parkhous@sfu.ca
authors.forename: Wade S
authors.initials: WS
authors.lastname: Parkhouse
authors.forename: Lori
authors.initials: L
authors.lastname: Cunningham
authors.forename: Ingrid
authors.initials: I
authors.lastname: McFee
authors.forename: Jennifer M Litt
authors.initials: JM
authors.lastname: Miller
authors.forename: Darryl
authors.initials: D
authors.lastname: Whitney
authors.forename: Steven L
authors.initials: SL
authors.lastname: Pelech
authors.forename: Charles
authors.initials: C
authors.lastname: Krieger
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000201:enzymology* / Q000235:genetics*; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D008297:Male; D051379:Mice; D008818:Mice, Neurologic Mutants; D008822:Mice, Transgenic; D009468:Neuromuscular Diseases / Q000201:enzymology / Q000235:genetics; D013482:Superoxide Dismutase / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D013482:Superoxide Dismutase