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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
Citation
Auderset, LF and Pitman, KA and Cullen, CL and Pepper, RE and Taylor, BV and Foa, L and Young, KM, 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, 8 Article 564351. ISSN 2296-634X (2020) [Refereed Article]
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Copyright Statement
Copyright 2020 The Authors. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY)
DOI: doi:10.3389/fcell.2020.564351
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 Details
| Item Type: | Refereed Article |
|---|---|
| Keywords: | LRP1, NG2 glia, alpha-2-macroglobulin, cuprizone, myelin, oligodendrocyte, proliferation, remyelination |
| Research Division: | Biomedical and Clinical Sciences |
| Research Group: | Neurosciences |
| Research Field: | Cellular nervous system |
| Objective Division: | Health |
| Objective Group: | Clinical health |
| Objective Field: | Diagnosis of human diseases and conditions |
| UTAS Author: | Auderset, LF (Mr Loic Auderset) |
| UTAS Author: | Pitman, KA (Dr Kimberley Pitman) |
| UTAS Author: | Cullen, CL (Dr Carlie Cullen) |
| UTAS Author: | Pepper, RE (Miss Renee Pepper) |
| UTAS Author: | Taylor, BV (Professor Bruce Taylor) |
| UTAS Author: | Foa, L (Professor Lisa Foa) |
| UTAS Author: | Young, KM (Associate Professor Kaylene Young) |
| ID Code: | 142036 |
| Year Published: | 2020 |
| Web of Science® Times Cited: | 6 |
| Deposited By: | Menzies Institute for Medical Research |
| Deposited On: | 2020-12-09 |
| Last Modified: | 2021-03-25 |
| Downloads: | 16 View Download Statistics |
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