title: Specific inhibition of secreted NRG1 types I-II by heparin enhances Schwann Cell myelination.
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.
authors.affiliation: Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, 76100, Israel.
authors.forename: Yael
authors.initials: Y
authors.lastname: Eshed-Eisenbach
authors.affiliation: Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, 76100, Israel.
authors.forename: Aaron
authors.initials: A
authors.lastname: Gordon
authors.affiliation: Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, 76100, Israel.
authors.forename: Natalya
authors.initials: N
authors.lastname: Sukhanov
authors.affiliation: Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, 76100, Israel.
authors.forename: Elior
authors.initials: E
authors.lastname: Peles
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D005727:Ganglia, Spinal / Q000166:cytology; D005786:Gene Expression Regulation / Q000187:drug effects; D006493:Heparin / Q000494:pharmacology*; D051379:Mice; D004676:Myelin Basic Protein / Q000378:metabolism; D009186:Myelin Sheath / Q000187:drug effects / Q000378:metabolism*; D009414:Nerve Growth Factors / Q000378:metabolism*; D020890:Neuregulin-1 / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects; D051381:Rats; D012583:Schwann Cells / Q000187:drug effects*; D013045:Species Specificity
chemical_list: D005343:Fibrinolytic Agents; D004676:Myelin Basic Protein; D009414:Nerve Growth Factors; D020890:Neuregulin-1; C490580:Nrg1 protein, rat; C491452:Nrg2 protein, rat; D006493:Heparin
keywords: PNS; Schwann cells; heparan sulfate proteoglycans; myelin; neuregulin