title: Sensorimotor and cognitive functions in a SOD1(G37R) transgenic mouse model of amyotrophic lateral sclerosis.
abstract: Amyotrophic lateral sclerosis (ALS) is a neurological disorder involving degeneration of motor neurons in brain and spinal cord, leading to progressive atrophy of skeletal muscles and, ultimately, paralysis and death. Copper-mediated oxidative damage is proposed to play a critical role in the pathogenesis of Cu/Zn superoxide dismutase (SOD1) - linked hereditary amyotrophic lateral sclerosis. To understand more clearly the pathogenesis of sensorimotor dysfunction and to find the most appropriate methods for early detection of symptoms and for monitoring them across time, a murine model was assessed at three time points (5, 8, and 11 months). Transgenic mice with the G37R mutation of human SOD1 exhibited earliest signs of dysfunction at 8 months in terms of a pathological hindpaw clasping reflex, as well as slowed movement time on a suspended bar, anomalies in footprint patterns, weaker grip strength, raised somatosensory thresholds, and deficits in passive avoidance learning, yielding a margin of 3-4 months before death to test experimental therapies.
authors.affiliation: Neurobehavioral Phenotyping Platform, CHUL Research Center (CHUQ) and Department of Molecular Medicine, Laval University, 2705 Laurier boul., Québec G1V 4G2, Canada. Mohammed.Filali@crchul.ulaval.ca
authors.forename: Mohammed
authors.initials: M
authors.lastname: Filali
authors.forename: Robert
authors.initials: R
authors.lastname: Lalonde
authors.forename: Serge
authors.initials: S
authors.lastname: Rivest
mesh_terms: D000367:Age Factors; D000690:Amyotrophic Lateral Sclerosis / Q000150:complications* / Q000235:genetics*; D000704:Analysis of Variance; D000818:Animals; D001362:Avoidance Learning / Q000502:physiology; D003072:Cognition Disorders / Q000209:etiology* / Q000235:genetics; D004195:Disease Models, Animal; D020233:Gait Disorders, Neurologic / Q000209:etiology* / Q000235:genetics; D018737:Hand Strength / Q000502:physiology; D019417:Hindlimb Suspension; D006801:Humans; D007738:Kyphosis / Q000209:etiology / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics*; D058748:Pain Perception / Q000502:physiology; D004856:Postural Balance / Q000235:genetics; D012018:Reflex / Q000235:genetics; D013482:Superoxide Dismutase / Q000235:genetics*; D000072105:Superoxide Dismutase-1
chemical_list: C000606290:SOD1 protein, human; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1