期刊
EXPERIMENTAL NEUROLOGY
卷 237, 期 2, 页码 304-311出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.expneurol.2012.07.011
关键词
Rolipram; PDE4 inhibitor; Demyelination; Remyelination; Oligodendrocyte precursor cell; Cuprizone; MAPK
资金
- Natural Science Foundation of Heilongjiang Province [LC08C08]
- China postdoctoral science foundation grant [20080430942]
Objective: Rolipram, a 3'-5'-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 methods: Cuprizone-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 2', 3'-cyclic nucleotide phosphodiesterase (CNPase) activity, MBP expression, and extracellular signal-regulated kinase (ERK) phosphorylation were measured. Results: Rolipram 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). Conclusion: Rolipram 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. (c) 2012 Elsevier Inc. All rights reserved.
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