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

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• 作者：Sold&aacute ; n ; M.Mateo Paz ; Warrington ; Arthur E. ; Bieber ; Allan J. ; Ciric ; Bogoljub ; Keulen ; Virginia Van ; et. al.
• 刊名：Molecular and Cellular Neuroscience
• 出版年：2003
• 出版时间：January, 2003
• 年：2003
• 卷：22
• 期：1
• 页码：14-24
• 全文大小：472 K

文摘

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.