Remyelination after cuprizone induced demyelination is accelerated in mice deficient in the polysialic acid synthesizing enzyme St8siaIV

Neuroscience. 2010 Nov 24;171(1):235-44. doi: 10.1016/j.neuroscience.2010.08.070. Epub 2010 Sep 15.

Abstract

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 wild-type 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Analysis of Variance
  • Animals
  • Animals, Newborn
  • Antigens / metabolism
  • Antigens, Differentiation / metabolism
  • Cell Count
  • Cell Differentiation / genetics
  • Cerebral Cortex / metabolism
  • Cerebral Cortex / pathology
  • Corpus Callosum / metabolism
  • Corpus Callosum / pathology
  • Cuprizone / toxicity*
  • Demyelinating Diseases / chemically induced*
  • Demyelinating Diseases / genetics
  • Demyelinating Diseases / pathology
  • Demyelinating Diseases / physiopathology*
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / genetics
  • Glial Fibrillary Acidic Protein / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Monoamine Oxidase Inhibitors / toxicity*
  • Myelin Basic Protein / metabolism
  • Myelin Proteins / metabolism
  • Myelin Proteolipid Protein / metabolism
  • Myelin-Associated Glycoprotein / genetics
  • Myelin-Associated Glycoprotein / metabolism
  • Myelin-Oligodendrocyte Glycoprotein
  • Neural Cell Adhesion Molecules / genetics
  • Neural Cell Adhesion Molecules / metabolism
  • Neuroglia / drug effects
  • Neuroglia / metabolism
  • Neurons / drug effects
  • Neurons / metabolism
  • Nogo Proteins
  • Proteoglycans / metabolism
  • Regeneration / genetics*
  • Sialic Acids / metabolism
  • Sialyltransferases / deficiency*

Substances

  • Antigens
  • Antigens, Differentiation
  • Glial Fibrillary Acidic Protein
  • Mog protein, mouse
  • Monoamine Oxidase Inhibitors
  • Myelin Basic Protein
  • Myelin Proteins
  • Myelin Proteolipid Protein
  • Myelin-Associated Glycoprotein
  • Myelin-Oligodendrocyte Glycoprotein
  • Neural Cell Adhesion Molecules
  • Nogo Proteins
  • Plp1 protein, mouse
  • Proteoglycans
  • Rtn4 protein, mouse
  • Sialic Acids
  • chondroitin sulfate proteoglycan 4
  • monocyte-macrophage differentiation antigen
  • polysialic acid
  • Cuprizone
  • Sialyltransferases