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

doi:10.1016/j.celrep.2021.109147

GluA2 overexpression in oligodendrocyte progenitors promotes postinjury oligodendrocyte regeneration

Cell Rep. 2021 May 18;35(7):109147. doi: 10.1016/j.celrep.2021.109147.

Authors

Rabia R Khawaja¹, Amit Agarwal², Masahiro Fukaya³, Hey-Kyeong Jeong⁴, Scott Gross⁵, Estibaliz Gonzalez-Fernandez⁴, Jonathan Soboloff⁵, Dwight E Bergles⁶, Shin H Kang⁷

Affiliations

¹ Center for Neural Repair and Rehabilitation (Shriners Hospitals of Pediatric Research Center), Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA; Department of Anatomy and Cell Biology, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA.
² The Solomon Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21025, USA; The Chica and Heinz Schaller Research Group, Institute for Anatomy and Cell Biology, Heidelberg University, 69120 Heidelberg, Germany; Interdisciplinary Center for Neurosciences, Heidelberg University, 69120 Heidelberg, Germany.
³ Department of Anatomy, Kitasato University School of Medicine, Sagamihara, Kanagawa 252-0374, Japan.
⁴ Center for Neural Repair and Rehabilitation (Shriners Hospitals of Pediatric Research Center), Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA.
⁵ Fels Cancer Institute for Personalized Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA.
⁶ The Solomon Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21025, USA; Kavli Neuroscience Discovery Institute, Johns Hopkins University, Baltimore, MD 21205, USA.
⁷ Center for Neural Repair and Rehabilitation (Shriners Hospitals of Pediatric Research Center), Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA; Department of Anatomy and Cell Biology, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA. Electronic address: [email protected].

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.

Keywords: AMPA receptor; GluA2; OPC; calcium; hypoxic-ischemia; injury; oligodendrocyte; remyelination.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Proliferation
Mice
Oligodendrocyte Precursor Cells / metabolism*
Oligodendroglia / metabolism*
Rats
Receptors, AMPA
Regeneration

Substances

Receptors, AMPA
glutamate receptor ionotropic, AMPA 2

Abstract

Publication types

MeSH terms

Substances

Grants and funding