Item Details

The Active Contribution of Oligodendrocyte Progenitor Cells to Neuroinflammation is Mediated by LRP1

Fernández-Castañeda, Anthony
Format
Thesis/Dissertation; Online
Author
Fernández-Castañeda, Anthony
Advisor
Gaultier, Alban
Abstract
Oligodendrocyte progenitor cells (OPCs) account for about 5% of total brain and spinal cord cells, giving rise to myelinating oligodendrocytes that provide electrical insulation to neurons of the CNS. OPCs have also recently been shown to regulate inflammatory responses and glial scar formation, suggesting functions that extend beyond myelination. Low-density lipoprotein receptor-related protein 1 (LRP1) is a multi-faceted phagocytic receptor that is highly expressed in several CNS cell types, including OPCs. Here, we have generated an oligodendroglia-specific knockout of LRP1, which presents with normal myelin development, but is associated with better outcomes in two animal models of demyelination (EAE and cuprizone). At a mechanistic level, LRP1 did not directly affect OPC differentiation into mature oligodendrocytes. Instead, animals lacking LRP1 in OPCs in the demyelinating CNS were characterized by a robust dampening of inflammation. In particular, LRP1-deficient OPCs presented with impaired antigen cross-presentation machinery, suggesting a failure to propagate the inflammatory response and thus promoting faster myelin repair and neuroprotection. Our study places OPCs as major regulators of neuroinflammation in an LRP1-dependent fashion.
Language
English
Published
University of Virginia, Neuroscience - School of Medicine, PHD (Doctor of Philosophy), 2019
Published Date
2019-11-30
Degree
PHD (Doctor of Philosophy)
Collection
Libra ETD Repository
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