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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Animals, Newborn
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Antibodies, Monoclonal / immunology
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Antibodies, Monoclonal / pharmacology*
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Antigens, Surface / drug effects
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Antigens, Surface / immunology
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Astrocytes / drug effects*
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Astrocytes / immunology
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Astrocytes / metabolism
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Calcium / metabolism*
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Calcium Signaling / drug effects*
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Calcium Signaling / immunology
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Cells, Cultured
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Demyelinating Diseases / drug therapy
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Demyelinating Diseases / immunology
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Demyelinating Diseases / metabolism
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Disease Models, Animal
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Endoplasmic Reticulum / drug effects
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Endoplasmic Reticulum / metabolism
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Female
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Glial Fibrillary Acidic Protein / metabolism
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Humans
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Mice
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Mice, Inbred Strains
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Myelin Sheath / immunology*
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Myelin Sheath / metabolism
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Oligodendroglia / drug effects*
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Oligodendroglia / immunology
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Oligodendroglia / metabolism
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Protein Binding / immunology
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Protein Structure, Tertiary / physiology
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Rats
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Rats, Sprague-Dawley
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Receptors, AMPA / antagonists & inhibitors
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Receptors, AMPA / metabolism
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Signal Transduction / drug effects*
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Signal Transduction / immunology
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Up-Regulation / drug effects
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Up-Regulation / immunology
Substances
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Antibodies, Monoclonal
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Antigens, Surface
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Glial Fibrillary Acidic Protein
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Receptors, AMPA
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Calcium