title: Glutamate uptake is decreased tardively in the spinal cord of FALS mice.
abstract: This study examined high affinity Na+-dependent uptake of glutamate in synaptosomal preparations from spinal cord in mice that express a dominant mutation of human copper/zinc superoxide dismutase (SOD1) and represent an animal model of amyotrophic lateral sclerosis (ALS). Their muscle strength was also monitored by a grip traction test throughout their lifespan. The high affinity Na+-dependent uptake of [3H]glutamate was decreased between 120 and 150 days of age. A marked and significant decrease in Vmax (-40.2%; p < 0.001) on whole spinal cord synaptosomes was observed at 150 days, with no change in Km. This significant decrease was reached a week before the animals died (157.2 +/- 2.2 days) and corresponded to a considerable fall in muscle strength (25% loss between 120 and 140 days, p < 0.001). The FALS mouse model therefore reproduces the decrease in glutamate uptake reported in humans suffering from sporadic or familial ALS. These results are discussed in terms of a possible tardive involvement of glutamate uptake deficiency in human ALS.
authors.affiliation: Rhône-Poulenc Rorer S.A., Centre de Recherche de Vitry-Alfortville, Service de neurophysiologie, Vitry-sur-Seine, France.
authors.forename: T
authors.initials: T
authors.lastname: Canton
authors.forename: J
authors.initials: J
authors.lastname: Pratt
authors.forename: J M
authors.initials: JM
authors.lastname: Stutzmann
authors.forename: A
authors.initials: A
authors.lastname: Imperato
authors.forename: A
authors.initials: A
authors.lastname: Boireau
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism*; D000818:Animals; D001693:Biological Transport, Active; D018698:Glutamic Acid / Q000378:metabolism*; D018737:Hand Strength / Q000502:physiology; D066298:In Vitro Techniques; D007700:Kinetics; D008526:Medulla Oblongata / Q000378:metabolism; D051379:Mice; D008818:Mice, Neurologic Mutants; D013116:Spinal Cord / Q000378:metabolism*; D016019:Survival Analysis; D013574:Synaptosomes / Q000378:metabolism
chemical_list: D018698:Glutamic Acid