کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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6018533 | 1186520 | 2012 | 8 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Rolipram promotes remyelination possibly via MEK-ERK signal pathway in cuprizone-induced demyelination mouse Rolipram promotes remyelination possibly via MEK-ERK signal pathway in cuprizone-induced demyelination mouse](/preview/png/6018533.png)
ObjectiveRolipram, a 3â²-5â²-cyclic adenosine monophosphate (cAMP)-dependent phosphodiesterase 4 (PDE4) inhibitor, has long been studied for its immune modulating effects in the treatment of experimental autoimmune encephalomyelitis (EAE). In the current study, we investigated the effects of rolipram on remyelination after cuprizone- or lysolecithin-induced demyelination and the signal transduction pathways potentially modulating this response.Materials and methodsCuprizone-induced demyelination in mice and lysolecithin (LPC)-induced demyelination in rat cerebellum slice culture were treated with rolipram. Demyelination was evaluated by Luxol fast blue (LFB) or myelin basic protein (MBP) staining and western blot. Oligodendroglial cells were cultured with different concentrations of rolipram, and 2â², 3â²-cyclic nucleotide phosphodiesterase (CNPase) activity, MBP expression, and extracellular signal-regulated kinase (ERK) phosphorylation were measured.ResultsRolipram antagonized lysolecithin (LPC)-induced demyelination in rat cerebellar slice cultures and cuprizone-fed mice. In vitro, rolipram treatment promoted oligodendrocyte precursor cell (OPC) maturation, an effect that was partially blocked by the inhibitors of the mitogen activated protein kinase kinase (MEK).ConclusionRolipram promotes the maturation of OPCs, facilitates remyelination, and increases ERK phosphorylation. All of these actions are involved in an action against cuprizone-induced demyelination that may occur partly via the MEK-ERK pathway. Importantly, this may have therapeutic implications for MS.
⺠Rolipram promotes remyelination in demyelinating mouse. ⺠Our study highlights the possibility that MS may be treated with rolipram. ⺠Rolipram promotes the maturation of OPCs, facilitates remyelination.
Journal: Experimental Neurology - Volume 237, Issue 2, October 2012, Pages 304-311