GluA2 overexpression in oligodendrocyte progenitors promotes postinjury oligodendrocyte regeneration

Cell Reports

Amit Agarwal¹  Scott Gross²  Hey-Kyeong Jeong³  Jonathan Soboloff⁴  Shin H. Kang⁴  Rabia R. Khawaja⁴  Estibaliz Gonzalez-Fernandez⁵  Dwight E. Bergles⁶  Masahiro Fukaya⁷ 

[1] Department of Anatomy and Cell Biology, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA;Interdisciplinary Center for Neurosciences, Heidelberg University, 69120 Heidelberg, Germany;The Chica and Heinz Schaller Research Group, Institute for Anatomy and Cell Biology, Heidelberg University, 69120 Heidelberg, Germany;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, Kitasato University School of Medicine, Sagamihara, Kanagawa 252-0374, Japan;Fels Cancer Institute for Personalized Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA;The Solomon Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21025, USA;

关键词: oligodendrocyte;    OPC;    GluA2;    remyelination;    AMPA receptor;    injury;   

DOI  :  

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown