The p38α MAPK Deletion in Oligodendroglia does not Attenuate Myelination Defects in a Mouse Model of Periventricular Leukomalacia

Seung H. Chung, Sangita Biswas, Jiho Sohn, Peng Jiang, Samaneh Dehghan, Hassan Marzban, Wenbin Deng

Research output: Contribution to journalArticle

Abstract

Periventricular leukomalacia (PVL) is a severe type of white matter damage in premature infants and the most common cause of cerebral palsy. It is generally known to be caused by hypoxia and inflammation. Currently there is no effective treatment available, in part due to that the pathogenesis of the disease has not been well understood. The p38α mitogen-activated protein kinase (MAPK) is the serine/threonine kinase and several in vitro studies demonstrated that p38 MAPK is essential for oligodendroglial differentiation and myelination. Indeed, our nerve/glial antigen 2 (NG2)-specific oligodendroglial p38α MAPK conditional knockout (CKO) mice revealed its complex roles in myelination and remyelination. To identify the specific in vivo roles of oligodendroglial p38α MAPK in PVL, we generated a mouse PVL model by combination of LPS-mediated inflammation and hypoxia–ischemia in NG2-p38α MAPK CKO mice. Our results demonstrate that a selective deletion of p38α MAPK in oligodendrocyte did not attenuate myelination defects in the mouse model of PVL. Myelination phenotype revealed by MBP immunostaining was not significantly affected in the p38α MAPK CKO mice compared to the wildtype after PVL induction. The electron microscopic images demonstrated that the microstructure of myelin structures was not significantly different between the wild-type and p38α MAPK CKO mice. In addition, oligodendrocyte degeneration in the corpus callosum white matter area was unaffected in the p38α MAPK CKO during and after the PVL induction. These data indicate that p38α MAPK in oligodendrocyte has minimal effect on myelination and oligodendrocyte survival in the mouse PVL model.

Original languageEnglish (US)
Pages (from-to)175-181
Number of pages7
JournalNeuroscience
Volume386
DOIs
StatePublished - Aug 21 2018

Keywords

  • myelination
  • oligodendrocyte
  • p38alpha MAPK
  • periventricular leukomalacia

ASJC Scopus subject areas

  • Neuroscience(all)

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