Objective: We examined expression of aryl hydrocarbon receptor nuclear translocator 2 (ARNT2), a basic-loop-helix transcription factor implicated in neuronal development and axonal health, in oligodendrocyte (OL) cultures and over the course of chronic experimental autoimmune encephalomyelitis (EAE), the murine model of multiple sclerosis (MS).
Methods: We assessed OL ARNT2 expression in EAE compared with sham-immunized controls and also in OL primary cultures and over the course of dibutyryl cyclic adenosine monophosphate (dbcAMP)-mediated maturation of the immortalized Oli-neu cell line. We also tested the functional role of ARNT2 in influencing OL characteristics using small interfering RNA (siRNA).
Results: ARNT2 is localized to Olig2 cells in healthy spinal cord gray and white matter. Despite a significant expansion of Olig2 cells in the white matter at peak disease, ARNT2 is reduced by almost half in OLs, along with a reduction in the percentage of ARNT2/Olig2 cells. Mature OLs in mixed cortical cultures or OLs matured from embryonic progenitors express negligible ARNT2. Similarly, Oli-neu cells express high levels of ARNT2, which are reduced following dbcAMP maturation. siRNA-mediated knockdown of ARNT2 affected OL viability, which led to an enrichment of myelin-producing OLs.
Conclusion: The analysis of ARNT2 expression in OLs demonstrates that OL ARNT2 expression is altered in EAE and during OL maturation. Findings point to ARNT2 as an important mediator of OL viability and differentiation and warrant further characterization as a target for intervention in demyelinating disorders such as MS.
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http://dx.doi.org/10.1212/NXI.0000000000000745 | DOI Listing |
J Appl Toxicol
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Graduate School of Maritime Science, Kobe University, Kobe, Japan.
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Center for Developmental Biology and Regenerative Medicine, Seattle Children's Research Institute, Seattle, WA, United States; Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, United States; Department of Pediatrics, University of Washington, Seattle, WA, United States.
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September 2024
Center for Cognition and Sociality, Institute for Basic Science, Daejeon 34126, South Korea. Electronic address:
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View Article and Find Full Text PDFbioRxiv
May 2024
Center for Developmental Biology and Regenerative Medicine, Seattle Children's Research Institute, Seattle, WA, United States.
Background: Vitamin D is a hormone regulating gene transcription. Prenatal vitamin D has been linked to immune and vascular function in the placenta, a key organ of pregnancy. To date, studies of vitamin D and placental gene expression have focused on a limited number of candidate genes.
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