APOE Inhibition of Remyelination and Regulation of OPC differentiation

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  • May 4, 2021
Creator
  • Elssner, Isabel
    • Affiliation: College of Arts and Sciences, Department of Biology
    • Other Affiliation: UNC Neuroscience Center
Abstract
  • Apolipoprotein E (APOE) interacts with the lipoprotein receptor to transport lipoproteins and facilitates ingestion of apoptotic cells, also known as efferocytosis. APOE-deficient macrophages ingest fewer apoptotic cells than wildtype cells. Because apoptotic cells are found in lesions of demyelination, we speculated that APOE and efferocytosis may be involved in remyelination. Our hypothesis is that APOE regulates OPC differentiation via the microglia secretome. To test this hypothesis, we assessed remyelination in vivo using APOE-/-, APOE2, APOE3, and APOE4 knock-in mice and in vitro using the OPC differentiation assay. In vivo, we found APOE3 mice showed delayed remyelination at the 5+2 week time point, but by 5+3 week the APOE3 variant was similar to WT. This indicates that APOE3 partly inhibits the remyelination process. Furthermore, it was found that APOE-/- had significantly more remyelination than other genotypes at the 5+1 time point, which suggests murine APOE inhibits remyelination temporarily. In vitro, the OPC differentiation assay showed that APOE3 and APOE-/- macrophage secretomes retained significantly more round and primary processes than the positive control indicating there were less factors driving initial cell differentiation. This suggests that murine APOE is required for efferocytosis and secretome content, but APOE3 may inhibit efferocytosis and alter the beneficial factors for OPC differentiation.
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  • In Copyright
Advisor
  • Matsushima, Glenn
    • Affiliation: College of Arts and Sciences, Department of Biology
    • Other Affiliation: UNC Neuroscience Center
Degree
  • Bachelor of Science
Graduation year
  • 2021
Language
  • English

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