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GluA2 overexpression in oligodendrocyte progenitors promotes postinjury oligodendrocyte regeneration

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 uncl...

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Main Authors: Khawaja, Rabia R. (Author) , Agarwal, Amit (Author) , Fukaya, Masahiro (Author) , Jeong, Hey-Kyeong (Author) , Gross, Scott (Author) , Gonzalez-Fernandez, Estibaliz (Author) , Soboloff, Jonathan (Author) , Bergles, Dwight E. (Author) , Kang, Shin H. (Author)
Format: Article (Journal)
Language:English
Published: 18 May 2021
In: Cell reports
Year: 2021, Volume: 35, Issue: 7, Pages: 1-15, e1-e6
ISSN:2211-1247
DOI:10.1016/j.celrep.2021.109147
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.celrep.2021.109147
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S2211124721004861
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Author Notes:Rabia R. Khawaja, Amit Agarwal, Masahiro Fukaya, Hey-Kyeong Jeong, Scott Gross, Estibaliz Gonzalez-Fernandez, Jonathan Soboloff, Dwight E. Bergles, and Shin H. Kang
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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.
Item Description:Gesehen am 11.08.2021
Physical Description:Online Resource
ISSN:2211-1247
DOI:10.1016/j.celrep.2021.109147

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