Remyelination-promoting antibodies activate distinct Ca2+ influx pathways in astrocytes and oligodendrocytes: Relationship to the mechanism of myelin repair

M. Mateo Paz Soldán, Arthur E. Warrington, Allan J. Bieber, Bogoljub Ciric, Virginia Van Keulen, Larry R. Pease, Moses Rodriguez

Research output: Contribution to journalArticlepeer-review

64 Scopus citations

Abstract

Our laboratory has identified mouse and human monoclonal antibodies that promote myelin repair in multiple models of demyelinating disease. We have proposed that these antibodies promote remyelination by directly activating central nervous system glia. Intracellular calcium concentration was monitored using a Fura2 ratiometric assay. Repair-promoting antibodies induced distinct Ca2+ signals in both astrocytes and oligodendrocytes. Astrocyte Ca2+ signaling is mediated by a phospholipase C-dependent pathway while oligodendrocyte Ca2+ signaling is mediated via AMPA-sensitive glutamate receptors. An antibody's ability to induce Ca2+ signals is statistically correlated with promotion of myelin repair. These findings support the hypothesis that remyelination-promoting antibodies are acting directly at the surface of glial cells to induce calcium-dependent physiologic reparative function.

Original languageEnglish (US)
Pages (from-to)14-24
Number of pages11
JournalMolecular and Cellular Neuroscience
Volume22
Issue number1
DOIs
StatePublished - Jan 1 2003

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Cell Biology

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