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Publication : Synaptic sprouting increases the uptake capacities of motoneurons in amyotrophic lateral sclerosis mice.

First Author  Millecamps S Year  2001
Journal  Proc Natl Acad Sci U S A Volume  98
Issue  13 Pages  7582-7
PubMed ID  11404466 Mgi Jnum  J:70621
Mgi Id  MGI:2137849 Doi  10.1073/pnas.131031098
Citation  Millecamps S, et al. (2001) Synaptic sprouting increases the uptake capacities of motoneurons in amyotrophic lateral sclerosis mice. Proc Natl Acad Sci U S A 98(13):7582-7
abstractText  Using adenoviruses encoding reporter genes as retrograde tracers, we assessed the capacity of motoneurons to take up and retrogradely transport adenoviral particles injected into the muscles of transgenic mice expressing the G93A human superoxide dismutase mutation, a model of amyotrophic lateral sclerosis. Surprisingly, transgene expression in the motoneurons was significantly higher in symptomatic mice than in control or presymptomatic mice. Using botulinum toxin to induce nerve sprouting at neuromuscular junctions, we showed that the unexpectedly high level of motoneurons retrograde transduction results, at least in part, from newly acquired uptake properties of the sprouts. These findings demonstrate the remarkable uptake properties of amyotrophic lateral sclerosis motoneurons in response to denervation and the rationale of using intramuscular injections of adenoviruses to overexpress therapeutic proteins in motor neuron diseases.
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