Protease activated receptor 2 controls myelin development, resiliency and repair

Hyesook Yoon, Maja Radulovic, Grant Walters, Alex R. Paulsen, Kristen Drucker, Phillip Starski, Jianmin Wu, David P. Fairlie, Isobel A. Scarisbrick

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Oligodendrocytes are essential regulators of axonal energy homeostasis and electrical conduction and emerging target cells for restoration of neurological function. Here we investigate the role of protease activated receptor 2 (PAR2), a unique protease activated G protein-coupled receptor, in myelin development and repair using the spinal cord as a model. Results demonstrate that genetic deletion of PAR2 accelerates myelin production, including higher proteolipid protein (PLP) levels in the spinal cord at birth and higher levels of myelin basic protein and thickened myelin sheaths in adulthood. Enhancements in spinal cord myelin with PAR2 loss-of-function were accompanied by increased numbers of Olig2- and CC1-positive oligodendrocytes, as well as in levels of cyclic adenosine monophosphate (cAMP), and extracellular signal related kinase 1/2 (ERK1/2) signaling. Parallel promyelinating effects were observed after blocking PAR2 expression in purified oligodendrocyte cultures, whereas inhibiting adenylate cyclase reversed these effects. Conversely, PAR2 activation reduced PLP expression and this effect was prevented by brain derived neurotrophic factor (BDNF), a promyelinating growth factor that signals through cAMP. PAR2 knockout mice also showed improved myelin resiliency after traumatic spinal cord injury and an accelerated pattern of myelin regeneration after focal demyelination. These findings suggest that PAR2 is an important controller of myelin production and regeneration, both in the developing and adult spinal cord.

Original languageEnglish (US)
Pages (from-to)2070-2086
Number of pages17
JournalGlia
Volume65
Issue number12
DOIs
StatePublished - Dec 2017

Keywords

  • development
  • myelination
  • oligodendrocyte
  • remyelination

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience

Fingerprint Dive into the research topics of 'Protease activated receptor 2 controls myelin development, resiliency and repair'. Together they form a unique fingerprint.

  • Cite this

    Yoon, H., Radulovic, M., Walters, G., Paulsen, A. R., Drucker, K., Starski, P., Wu, J., Fairlie, D. P., & Scarisbrick, I. A. (2017). Protease activated receptor 2 controls myelin development, resiliency and repair. Glia, 65(12), 2070-2086. https://doi.org/10.1002/glia.23215