title: Ghrelin inhibits oligodendrocyte cell death by attenuating microglial activation.
abstract: BACKGROUND
  Recently, we reported the antiapoptotic effect of ghrelin in spinal cord injury-induced apoptotic cell death of oligodendrocytes. However, how ghrelin inhibits oligodendrocytes apoptosis, is still unknown. Therefore, in the present study, we examined whether ghrelin inhibits microglia activation and thereby inhibits oligodendrocyte apoptosis.
  
  
  METHODS
  Using total cell extracts prepared from BV-2 cells activated by lipopolysaccharide (LPS) with or without ghrelin, the levels of p-p38 phosphor-p38 mitogen-activated protein kinase (p-p38MAPK), phospho-c-Jun N-terminal kinase (pJNK), p-c-Jun, and pro-nerve growth factor (proNGF) were examined by Western blot analysis. Reactive oxygen species (ROS) production was investigated by using dichlorodihydrofluorescein diacetate. To examine the effect of ghrelin on oligodendrocyte cell death, oligodendrocytes were cocultured in transwell chambers of 24-well plates with LPS-stimulated BV-2 cells. After 48 hours incubation, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and terminal deoxynucleotidyl transferase 2'-deoxyuridine, 5'-triphosphate nick end labeling staining were assessed.
  
  
  RESULTS
  Ghrelin treatment significantly decreased levels of p-p38MAPK, p-JNK, p-c-Jun, and proNGF in LPS-stimulated BV-2 cells. ROS production increased in LPS-stimulated BV-2 cells was also significantly inhibited by ghrelin treatment. In addition, ghrelin significantly inhibited oligodendrocyte cell death when cocultured with LPS-stimulated BV-2 cells.
  
  
  CONCLUSIONS
  Ghrelin inhibits oligodendrocyte cell death by decreasing proNGF and ROS production as well as p38MAPK and JNK activation in activated microglia as an anti-inflammatory hormone.
authors.affiliation: Age-Related and Brain Diseases Research Center, Kyung Hee University School of Medicine, Seoul, Korea.
authors.forename: Jee Youn
authors.initials: JY
authors.lastname: Lee
authors.affiliation: Age-Related and Brain Diseases Research Center, Kyung Hee University School of Medicine, Seoul, Korea. ; Department of Biochemistry and Molecular Biology, Kyung Hee University School of Medicine, Seoul, Korea.
authors.forename: Tae Young
authors.initials: TY
authors.lastname: Yune
keywords: BV-2 microglia cell; Ghrelin; Oligodendroglia; Pro-nerve growth factor; Reactive oxygen species; c-Jun N-terminal kinase; p38MAPK