RT Journal Article
SR Electronic
T1 Dysmyelinated Lower Motor Neurons Retract and Regenerate Dysfunctional Synaptic Terminals
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 3890
OP 3898
DO 10.1523/JNEUROSCI.4617-03.2004
VO 24
IS 15
A1 Xinghua Yin
A1 Grahame J. Kidd
A1 Erik P. Pioro
A1 Jennifer McDonough
A1 Ranjan Dutta
A1 M. Laura Feltri
A1 Lawrence Wrabetz
A1 Albee Messing
A1 Ryan M. Wyatt
A1 Rita J. Balice-Gordon
A1 Bruce D. Trapp
YR 2004
UL http://www.jneurosci.org/content/24/15/3890.abstract
AB 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.