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
Affiliations
Rabia R. Khawaja
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
Amit Agarwal
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
Masahiro Fukaya
Department of Anatomy, Kitasato University School of Medicine, Sagamihara, Kanagawa 252-0374, Japan
Hey-Kyeong Jeong
Center for Neural Repair and Rehabilitation (Shriners Hospitals of Pediatric Research Center), Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA
Scott Gross
Fels Cancer Institute for Personalized Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA
Estibaliz Gonzalez-Fernandez
Center for Neural Repair and Rehabilitation (Shriners Hospitals of Pediatric Research Center), Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA
Jonathan Soboloff
Fels Cancer Institute for Personalized Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA
Dwight E. Bergles
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
Shin H. Kang
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; Corresponding author
Summary: 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.
