Dysmyelinated Lower Motor Neurons Retract and Regenerate Dysfunctional Synaptic Terminals

Department of Neurosciences, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience (Impact Factor: 6.34). 05/2004; 24(15):3890-8. DOI: 10.1523/JNEUROSCI.4617-03.2004
Source: PubMed


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.

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    • "r junction of treated animals contribute to the clinical improvement in the mice and perhaps also to the increased num - bers of large - diameter axons in the treated nerves . Demyelinated axons have been shown to impair the regeneration of nerve ter - minals , resulting in dysfunctional presynaptic neuromuscular junc - tion following retraction ( Yin et al . , 2004 ) . At post - natal Day 13 when the neuromuscular junctions are still in a highly plastic phase ( Brill et al . , 2011 ) , the deficits are not yet pronounced , but they become gradually aggravated with ageing . Normally functioning neuromuscular junction are necessary to provide retrograde trans - port from muscle to the neuronal cell "
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    • "In addition, retraction of nerve terminals increased over ten-fold at PSC-ablated NMJs (Reddy et al., 2003). A similar dependence of axon terminal stability from MSCs has been observed in various dysmyelinating axon pathologies (Scherer, 1999; Martini, 2001; Yin et al., 2004). The analogous experiment to PSC ablation at the mammalian NMJ requires injection of a subset of anti-disialosyl antibodies to selectively remove TSCs. "
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