GluA2 overexpression in oligodendrocyte progenitors promotes postinjury oligodendrocyte regeneration

Rabia R. Khawaja, Amit Agarwal, Masahiro Fukaya, Hey Kyeong Jeong, Scott Gross, Estibaliz Gonzalez-Fernandez, Jonathan Soboloff, Dwight E. Bergles, Shin H. Kang

Research output: Contribution to journalArticlepeer-review

Abstract

Oligodendrocyte precursor cells (OPCs) are essential for developmental myelination and oligodendrocyte regeneration after CNS injury. These progenitors express calcium-permeable AMPA receptors (AMPARs) and form direct synapses with neurons throughout the CNS, but the roles of this signaling are unclear. To enable selective alteration of the properties of AMPARs in oligodendroglia, we generate mice that allow cell-specific overexpression of EGFP-GluA2 in vivo. In healthy conditions, OPC-specific GluA2 overexpression significantly increase their proliferation in an age-dependent manner but did not alter their rate of differentiation into oligodendrocytes. In contrast, after demyelinating brain injury in neonates or adults, higher GluA2 levels promote both OPC proliferation and oligodendrocyte regeneration, but do not prevent injury-induced initial cell loss. These findings indicate that AMPAR GluA2 content regulates the proliferative and regenerative behavior of adult OPCs, serving as a putative target for better myelin repair.

Original languageEnglish (US)
Article number109147
JournalCell Reports
Volume35
Issue number7
DOIs
StatePublished - May 18 2021

Keywords

  • AMPA receptor
  • GluA2
  • OPC
  • calcium
  • hypoxic-ischemia
  • injury
  • oligodendrocyte
  • remyelination

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Fingerprint

Dive into the research topics of 'GluA2 overexpression in oligodendrocyte progenitors promotes postinjury oligodendrocyte regeneration'. Together they form a unique fingerprint.

Cite this