Thymosin beta4 promotes oligodendrogenesis in the demyelinating central nervous system
Abstract
Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS). No effective remyelination therapies are in use. We hypothesized that thymosin beta4 (Tβ4) is an effective remyelination treatment by promoting differentiation of oligodendrocyte progenitor cells (OPCs), and that the epidermal growth factor receptor (EGFR) signaling pathway contributes to this process. Two demyelination animal models were employed in this study: 1) experimental autoimmune encephalomyelitis (EAE), an animal model of MS. EAE mice were treated daily for 30days, with Tβ4 or saline treatment initiated on the day of EAE onset; and 2) cuprizone diet model, a non-inflammatory demyelination model. The mice were treated daily for 4weeks with Tβ4 or saline after fed a cuprizone diet for 5weeks. Immunofluorescent staining and Western blot were performed to measure the differentiation of OPCs, myelin and axons, respectively. To obtain insight into mechanisms of action, the expression and activation of the EGFR pathway was measured. AG1478, an EGFR inhibitor, was employed in a loss-of-function study. Data revealed that animals in both demyelination models exhibited significant reduction of myelin basic protein (MBP(+)) levels and CNPase(+...Continue Reading
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