title: Dysmyelinated lower motor neurons retract and regenerate dysfunctional synaptic terminals.
abstract: Axonal degeneration is the major cause of permanent neurological disability in individuals with inherited diseases of myelin. Axonal and neuronal changes that precede axonal degeneration, however, are not well characterized. We show here that dysmyelinated lower motor neurons retract and regenerate dysfunctional presynaptic terminals, leading to severe neurological disability before axonal degeneration. In addition, dysmyelination led to a decreased synaptic quantal content, an indicator of synaptic dysfunction. The amplitude and rise time of miniature endplate potentials were also increased, but these changes were primarily consistent with an increase in the passive membrane properties of the transgenic muscle fibers. Maintenance of synaptic connections should be considered as a therapeutic target for slowing progression of neurological disability in primary diseases of myelin.
authors.affiliation: Department of Neurosciences, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
authors.forename: Xinghua
authors.initials: X
authors.lastname: Yin
authors.forename: Grahame J
authors.initials: GJ
authors.lastname: Kidd
authors.forename: Erik P
authors.initials: EP
authors.lastname: Pioro
authors.forename: Jennifer
authors.initials: J
authors.lastname: McDonough
authors.forename: Ranjan
authors.initials: R
authors.lastname: Dutta
authors.forename: M Laura
authors.initials: ML
authors.lastname: Feltri
authors.forename: Lawrence
authors.initials: L
authors.lastname: Wrabetz
authors.forename: Albee
authors.initials: A
authors.lastname: Messing
authors.forename: Ryan M
authors.initials: RM
authors.lastname: Wyatt
authors.forename: Rita J
authors.initials: RJ
authors.lastname: Balice-Gordon
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Trapp
mesh_terms: D000818:Animals; D003711:Demyelinating Diseases / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D004185:Disability Evaluation; D004195:Disease Models, Animal; D018450:Disease Progression; D004576:Electromyography; D015417:Hereditary Sensory and Motor Neuropathy / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D051379:Mice; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000473:pathology / Q000502:physiology*; D018482:Muscle, Skeletal / Q000294:innervation / Q000503:physiopathology; D009133:Muscular Atrophy / Q000473:pathology; D018993:Myelin P0 Protein / Q000096:biosynthesis / Q000235:genetics; D009416:Nerve Regeneration / Q000235:genetics; D009469:Neuromuscular Junction / Q000473:pathology / Q000503:physiopathology*; D017729:Presynaptic Terminals / Q000473:pathology / Q000502:physiology*; D012583:Schwann Cells / Q000378:metabolism / Q000473:pathology; D009435:Synaptic Transmission; D013572:Synaptic Vesicles / Q000378:metabolism / Q000473:pathology
chemical_list: D018993:Myelin P0 Protein