title: Activity-driven synaptic and axonal degeneration in canine motor neuron disease.
abstract: The role of neuronal activity in the pathogenesis of neurodegenerative disease is largely unknown. In this study, we examined the effects of increasing motor neuron activity on the pathogenesis of a canine version of inherited motor neuron disease (hereditary canine spinal muscular atrophy). Activity of motor neurons innervating the ankle extensor muscle medial gastrocnemius (MG) was increased by denervating close synergist muscles. In affected animals, 4 wk of synergist denervation accelerated loss of motor-unit function relative to control muscles and decreased motor axon conduction velocities. Slowing of axon conduction was greatest in the most distal portions of motor axons. Morphological analysis of neuromuscular junctions (NMJs) showed that these functional changes were associated with increased loss of intact innervation and with the appearance of significant motor axon and motor terminal sprouting. These effects were not observed in the MG muscles of age-matched, normal animals with synergist denervation for 5 wk. The results indicate that motor neuron action potential activity is a major contributing factor to the loss of motor-unit function and degeneration in inherited canine motor neuron disease.
authors.affiliation: Department of Physiology, Emory University School of Medicine, 615 Michael Street, Atlanta, GA 30322, USA.
authors.forename: Dario I
authors.initials: DI
authors.lastname: Carrasco
authors.forename: Mark M
authors.initials: MM
authors.lastname: Rich
authors.forename: Qingbo
authors.initials: Q
authors.lastname: Wang
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Cope
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Pinter
mesh_terms: D000818:Animals; D001369:Axons; D004285:Dogs; D009045:Motor Endplate / Q000503:physiopathology; D009046:Motor Neurons; D009121:Muscle Denervation; D018482:Muscle, Skeletal / Q000294:innervation; D009134:Muscular Atrophy, Spinal / Q000235:genetics / Q000503:physiopathology*; D009410:Nerve Degeneration; D009416:Nerve Regeneration; D009431:Neural Conduction; D016900:Neurofilament Proteins / Q000378:metabolism; D009469:Neuromuscular Junction / Q000503:physiopathology; D013569:Synapses; D013643:Tarsus, Animal; D013997:Time Factors
chemical_list: D016900:Neurofilament Proteins