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01.09.2011 | Original Paper

The spinal muscular atrophy mouse model, SMAΔ7, displays altered axonal transport without global neurofilament alterations

verfasst von: Jeffrey M. Dale, Hailian Shen, Devin M. Barry, Virginia B. Garcia, Ferrill F. Rose Jr, Christian L. Lorson, Michael L. Garcia

Erschienen in: Acta Neuropathologica | Ausgabe 3/2011

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Abstract

Spinal muscular atrophy (SMA) is a neurodegenerative disease resulting from decreased levels of survival motor neuron 1 (SMN1) protein. Reduced SMN1 levels are linked to pathology at neuromuscular junctions (NMJs), which includes decreased vesicle density and organization, decreased quantal release, increased endplate potential duration, and neurofilament (NF) accumulations. This work presents a first study towards defining molecular alterations that may lead to the development of NMJ pathology in SMA. Fast, anterograde transport of synaptic vesicle 2 (SV2-c) and synaptotagmin (Syt1) proteins was reduced 2 days prior to the observed decrease in synaptic vesicle density. Moreover, reduced accumulation of SV2-c or Syt1 was not due to reduced protein expression or reduced kinesin activity. Dynein levels were reduced at times that are consistent with NF accumulations at NMJs. Furthermore, NF distribution, from cell body to sciatic nerve, appeared normal in SMA∆7 mice. Taken together, these results suggest that reduced axonal transport may provide a mechanistic explanation for reduced synaptic vesicle density and concomitant synaptic transmission defects, while providing evidence that suggests NF accumulations result from local NMJ alterations to NFs.

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Titel: The spinal muscular atrophy mouse model, SMAΔ7, displays altered axonal transport without global neurofilament alterations
verfasst von: Jeffrey M. Dale
Hailian Shen
Devin M. Barry
Virginia B. Garcia
Ferrill F. Rose Jr
Christian L. Lorson
Michael L. Garcia
Publikationsdatum: 01.09.2011
Verlag: Springer-Verlag
Erschienen in: Acta Neuropathologica / Ausgabe 3/2011
Print ISSN: 0001-6322
Elektronische ISSN: 1432-0533
DOI: https://doi.org/10.1007/s00401-011-0848-5

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