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Low-density lipoprotein receptor-related protein 1 (LRP1) is a negative regulator of oligodendrocyte progenitor cell differentiation in the adult mouse brain

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Auderset, L, Pitman, KA ORCID: 0000-0003-3198-9336, Cullen, CL ORCID: 0000-0001-6929-6258, Pepper, RE, Taylor, BV, Foa, L ORCID: 0000-0003-4131-8341 and Young, KM ORCID: 0000-0002-1686-3463 2020 , 'Low-density lipoprotein receptor-related protein 1 (LRP1) is a negative regulator of oligodendrocyte progenitor cell differentiation in the adult mouse brain' , Frontiers in Cell and Developmental Biology, vol. 8 , pp. 1-24 , doi: 10.3389/fcell.2020.564351.

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Abstract

Low-density lipoprotein receptor-related protein 1 (LRP1) is a large, endocytic cell surface receptor that is highly expressed by oligodendrocyte progenitor cells (OPCs) and LRP1 expression is rapidly downregulated as OPCs differentiate into oligodendrocytes (OLs). We report that the conditional deletion of Lrp1 from adult mouse OPCs (Pdgfrα-CreER :: Lrp1 fl/fl) increases the number of newborn, mature myelinating OLs added to the corpus callosum and motor cortex. As these additional OLs extend a normal number of internodes that are of a normal length, Lrp1-deletion increases adult myelination. OPC proliferation is also elevated following Lrp1 deletion in vivo, however, this may be a secondary, homeostatic response to increased OPC differentiation, as our in vitro experiments show that LRP1 is a direct negative regulator of OPC differentiation, not proliferation. Deleting Lrp1 from adult OPCs also increases the number of newborn mature OLs added to the corpus callosum in response to cuprizone-induced demyelination. These data suggest that the selective blockade of LRP1 function on adult OPCs may enhance myelin repair in demyelinating diseases such as multiple sclerosis.

Item Type: Article
Authors/Creators:Auderset, L and Pitman, KA and Cullen, CL and Pepper, RE and Taylor, BV and Foa, L and Young, KM
Keywords: LRP1, NG2 glia, alpha-2-macroglobulin, cuprizone, myelin, oligodendrocyte, proliferation, remyelination
Journal or Publication Title: Frontiers in Cell and Developmental Biology
Publisher: Frontiers Research Foundation
ISSN: 2296-634X
DOI / ID Number: 10.3389/fcell.2020.564351
Copyright Information:

Copyright 2020 The Authors. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY)

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