Low-density lipoprotein receptor-related protein 1 (LRP1) is a negative regulator of oligodendrocyte progenitor cell differentiation in the adult mouse brain
| Autor: | Lisa Foa, Renee E Pepper, Loic Auderset, Bruce V. Taylor, Kaylene M. Young, Carlie L. Cullen, Kimberley A Pitman |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
NG2 glia LRP1 proliferation Cellular differentiation Endocytic cycle Cell Biology Corpus callosum 03 medical and health sciences Cell and Developmental Biology Myelin 0302 clinical medicine Cell surface receptor medicine Remyelination lcsh:QH301-705.5 Original Research Cell Biology Oligodendrocyte cuprizone Cell biology myelin stomatognathic diseases 030104 developmental biology remyelination medicine.anatomical_structure lcsh:Biology (General) nervous system 030220 oncology & carcinogenesis LDL receptor oligodendrocyte alpha-2-macroglobulin Developmental Biology |
| Zdroj: | Frontiers in Cell and Developmental Biology Frontiers in Cell and Developmental Biology, Vol 8 (2020) |
| Popis: | 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 :: Lrp1fl/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. Graphical Abstract LRP1 regulates adult oligodendrogenesis and remyelination. |
| Databáze: | OpenAIRE |
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