title: Rolipram promotes remyelination possibly via MEK-ERK signal pathway in cuprizone-induced demyelination mouse.
abstract: 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.
  
  
  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).
  
  
  CONCLUSIONS
  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.
authors: Department of Neurology, the First Affiliated Hospital of Harbin Medical University, Ha'erbin 150001, China. Xiaojiasun@gmail.com
authors: Xiaojia
authors: X
authors: Sun
authors: Yuting
authors: Y
authors: Liu
authors: Boyang
authors: B
authors: Liu
authors: Zhicheng
authors: Z
authors: Xiao
authors: Liming
authors: L
authors: Zhang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects; D003471:Cuprizone / Q000633:toxicity; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D008244:Lysophosphatidylcholines / Q000633:toxicity; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D008996:Monoamine Oxidase Inhibitors / Q000633:toxicity; D009836:Oligodendroglia / Q000166:cytology / Q000187:drug effects; D009924:Organ Culture Techniques; D058988:Phosphodiesterase 4 Inhibitors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020889:Rolipram / Q000494:pharmacology*; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism
chemical_list: D008244:Lysophosphatidylcholines; D008996:Monoamine Oxidase Inhibitors; D058988:Phosphodiesterase 4 Inhibitors; D003471:Cuprizone; D020889:Rolipram