A2d1 as a novel molecular mediator regulating mature oligodendrocyte cell density
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Date
2024-05
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The Ohio State University
Abstract
Myelination, the process by which glial cells produce layers of myelin sheaths that wrap around neuronal axons and act as a layer of insulation for the transmission of action potentials, is essential for central nervous system (CNS) function. In the CNS, myelin sheaths are exclusively formed by oligodendrocytes, which are differentiated from oligodendrocyte precursor cells (OPCs). OPCs express abundant voltage-gated calcium channels (VGCCs), and these VGCCs are known to play a role in regulating myelination. Alpha2delta1 (A2d1) subunits, the auxiliary subunits of VGCCs, increase the membrane expression of VGCCs and subsequent Ca2+ current density. The goal of this study is to investigate how A2d1 subunits expressed in adult OPCs regulate the proliferation and differentiation of OPCs and the subsequent myelination. To knock out Cacna2d1, the gene encoding A2d1, in OPCs specifically, we crossed a tamoxifen-inducible PDGFRα-CreERT2 mouse line with Cacna2d1fl/fl mice to generate a double transgenic PDGFRα: Cacna2d1fl/fl line. In addition, we crossed the PDGFRα-CreERT2 with the TdTomato reporter mice (Ai9) to generate the control double transgenic PDGFRα:TdTomato line. Cacna2d1 was deleted in adult OPCs by administering tamoxifen in 8-week-old PDGFRα: Cacna2d1fl/fl mice (Cacna2d1KO group). We did not observe any alteration in the OPC proliferation rate via the BrdU incorporation assay. Interestingly, we saw an increase in mature oligodendrocyte density in Cacna2d1KO mice when compared to control mice. These results suggest that deleting A2d1 subunits in adult OPCs enhances oligodendrogenesis.
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Keywords
Oligodendrocyte, subunit, Myelin, Voltage-gated calcium channels