title: Neurotransmitter release in motor nerve terminals of a mouse model of mild spinal muscular atrophy.
abstract: Spinal muscular atrophy is a genetic disease which severity depends on the amount of SMN protein, the product of the genes SMN1 and SMN2. Symptomatology goes from severe neuromuscular impairment leading to early death in infants to slow progressing motor deficits during adulthood. Much of the knowledge about the pathophysiology of SMA comes from studies using genetically engineered animal models of the disease. Here we investigated one of the milder models, the homozygous A2G SMA mice, in which the level of the protein is restored to almost normal levels by the addition of a mutated transgene to the severe SMN-deficient background. We examined neuromuscular function and found that calcium-dependent neurotransmitter release was significantly decreased. In addition, the amplitude of spontaneous endplate potentials was decreased, the morphology of NMJ altered, and slight changes in short-term synaptic plasticity were found. In spite of these defects, excitation contraction coupling was well preserved, possibly due to the safety factor of this synapse. These data further support that the quasi-normal restoration of SMN levels in severe cases preserves neuromuscular function, even when neurotransmitter release is significantly decreased at motor nerve terminals. Nevertheless, this deficit could represent a greater risk of motor impairment during aging or after injuries.
authors.affiliation: Department of Medical Physiology and Biophysics School of Medicine, University of Seville, Seville, Spain.
authors.forename: Rocío
authors.initials: R
authors.lastname: Ruiz
authors.forename: Lucía
authors.initials: L
authors.lastname: Tabares
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D004195:Disease Models, Animal; D004576:Electromyography; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009045:Motor Endplate / Q000502:physiology; D009046:Motor Neurons / Q000378:metabolism*; D009134:Muscular Atrophy, Spinal / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D009469:Neuromuscular Junction / Q000473:pathology; D009473:Neuronal Plasticity / Q000502:physiology; D055533:Survival of Motor Neuron 1 Protein / Q000378:metabolism*; D013569:Synapses / Q000502:physiology
chemical_list: D055533:Survival of Motor Neuron 1 Protein
keywords: motor neuron; neurodegeneration; neuromuscular junction; spinal muscular atrophy; synapse