Journal
NEUROSCIENCE
Volume 171, Issue 1, Pages 235-244Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuroscience.2010.08.070
Keywords
myelin; polysialic acid; polysialyltransferases; C57BL/6J mice; cuprizone
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Funding
- Marie Curie Actions [MST-CT-2005 021014]
- State of Lower Saxony
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Polysialic acid (PSA) is a carbohydrate polymer added post-translationally on the neural cell adhesion molecule (NCAM) affecting its adhesion properties. It has been suggested that the presence of PSA in demyelinated lesions in multiple sclerosis could prevent axon-glia interactions inhibiting spontaneous remyelination. The enzyme St8siaIV is one of the two polysialyltransferases responsible for PSA synthesis, and it is predominantly active during adult life. Here we treated 8-10-weeks old St8siaIV deficient and wildtype mice for 5 weeks with cuprizone, which is a reliable model for de- and remyelination in the corpus callosum and cortex. Developmental myelination of the St8siaIV knock-out mice was not disturbed and adult mice showed normal myelin protein expression. Demyelination did not differ between transgenic and wild-type mice but early myelin protein re-expression and thus remyelination were accelerated in St8siaIV knock-out mice during the first week after withdrawal of the toxin. This was mainly due to enhanced oligodendrocyte precursor cells (OPC) differentiation and to a lesser extent to OPC recruitment. These data are proof of principle that PSA expression interferes at least to some extent with remyelination in vivo. (C) 2010 IBRO. Published by Elsevier Ltd. All rights reserved.
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