Altered sensorimotor development in a transgenic mouse model of amyotrophic lateral sclerosis.
Most neurodegenerative diseases become manifest at an adult age but abnormalities or pathological symptoms appear earlier. It is important to identify the initial mechanisms underlying such progressive neurodegenerative disease in both humans and animals. Transgenic mice expressing the familial amyotrophic lateral sclerosis (ALS)-linked mutation (G85R) in the enzyme superoxide dismutase 1 (SOD1) develop motor neuron disease at 8-10 months of age. We address the question of whether the mutation has an early impact on spinal motor networks in postnatal mutant mice. Behavioural tests showed a significant delay in righting and hind-paw grasping responses in mutant SOD1G85R mice during the first postnatal week, suggesting a transient motor deficit compared to wild-type mice. In addition, extracellular recordings from spinal ventral roots in an in vitro brainstem-spinal cord preparation demonstrated different pharmacologically induced motor activities between the two strains. Rhythmic motor activity was difficult to evoke with N-methyl-DL-aspartate and serotonin at the lumbar levels in SOD1G85R mice. In contrast to lumbar segments, rhythmic activity was similar in the sacral roots from the two strains. These results strongly support the fact that the G85R mutation may have altered lumbar spinal motor systems much earlier than previously recognized.
Amendola
Julien
J
CNRS UMR-6196, Plasticité et Physiopathologie de la Motricité, Université de la Méditerranée, 31 Chemin Joseph Aiguier, 13402 Marseille cedex 20, France.
Verrier
Bernard
B
Roubertoux
Pierre
P
Durand
Jacques
J
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000690:Amyotrophic Lateral Sclerosis / Q000503:physiopathology*; D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007839:Functional Laterality / Q000187:drug effects; D018737:Hand Strength / Q000502:physiology; D066298:In Vitro Techniques; D051379:Mice; D008822:Mice, Transgenic / Q000502:physiology*; D009043:Motor Activity / Q000502:physiology*; D009046:Motor Neurons / Q000145:classification / Q000187:drug effects / Q000502:physiology; D016202:N-Methylaspartate / Q000031:analogs & derivatives* / Q000494:pharmacology; D011597:Psychomotor Performance / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology; D013126:Spinal Nerve Roots / Q000166:cytology / Q000254:growth & development; D013482:Superoxide Dismutase / Q000235:genetics; D000072105:Superoxide Dismutase-1
C000606290:SOD1 protein, human; D012701:Serotonin; D016202:N-Methylaspartate; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; C083705:N-methyl-DL-aspartic acid