Specific inhibition of secreted NRG1 types I-II by heparin enhances Schwann Cell myelination

Glia. 2016 Jul;64(7):1227-34. doi: 10.1002/glia.22995. Epub 2016 May 3.

Abstract

Primary cultures of mixed neuron and Schwann cells prepared from dorsal root ganglia (DRG) are extensively used as a model to study myelination. These dissociated DRG cultures have the particular advantage of bypassing the difficulty in purifying mouse Schwann cells, which is often required when using mutant mice. However, the drawback of this experimental system is that it yields low amounts of myelin. Here we report a simple and efficient method to enhance myelination in vitro. We show that the addition of heparin or low molecular weight heparin to mixed DRG cultures markedly increases Schwann cells myelination. The myelin promoting activity of heparin results from specific inhibition of the soluble immunoglobulin (Ig)-containing isoforms of neuregulin 1 (i.e., NRG1 types I and II) that negatively regulates myelination. Heparin supplement provides a robust and reproducible method to increase myelination in a simple and commonly used culture system. GLIA 2016;64:1227-1234.

Keywords: PNS; Schwann cells; heparan sulfate proteoglycans; myelin; neuregulin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Embryo, Mammalian
  • Fibrinolytic Agents / pharmacology*
  • Ganglia, Spinal / cytology
  • Gene Expression Regulation / drug effects
  • Heparin / pharmacology*
  • Mice
  • Myelin Basic Protein / metabolism
  • Myelin Sheath / drug effects
  • Myelin Sheath / metabolism*
  • Nerve Growth Factors / metabolism*
  • Neuregulin-1 / metabolism*
  • Neurons / drug effects
  • Rats
  • Schwann Cells / drug effects*
  • Species Specificity

Substances

  • Fibrinolytic Agents
  • Myelin Basic Protein
  • Nerve Growth Factors
  • Neuregulin-1
  • Nrg1 protein, rat
  • Nrg2 protein, rat
  • Heparin