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Signal-Mediated Epigenetic Regulation of Oligodendrocyte Differentiation and Maturation via Alterations in Histone Acetylation Patterns: Implications for Multiple Sclerosis

Houston, Sara Ann

Abstract Details

2014, PHD, Kent State University, College of Arts and Sciences / School of Biomedical Sciences.
Oligodendrocytes are damaged in MS lesioned areas and myelin degeneration occurs. In remitting stages, attempts to remyelinate have been noted but unfortunately it tends to be less developed and frequently fails to be sustained. The cellular environment may be altered to an extent that these cells are unable to appropriately activate cellular programs required for proper differentiation and myelination. It is known that in MS cortex excessive excitatory transmitter availability occurs with increased glutamate levels and increased expression of glutamate receptors on oligodendrocytes. We set out to examine the impact that glutamate signaling plays in the development of OLs. In particular, we intended to link the glutamate-induced activation of several signaling intermediates with alterations is histone acetylation that results in alterations in the expression of mature OL proteins as well as the expression of transcription factors that might mediate their development. Through the use of cultured OPCs we were able to show that through AMPA and mGluR receptors, glutamate increases intracellular calcium levels and activates MAPK/Erk and cPLA2 signaling intermediates to phosphorylate and deactivate HDAC4 in order to increase acetylation at histone H3 causing an increased acetylation of histones in the chromatin associated with promoter regions of several important transcriptional repressors, Sox11 and Egr1. Thus, we suggest that this results in an increase in the expression of these noted repressors of OPC development inhibiting OPC differentiation and their ability to remyelinate at MS lesions.
Ernest Freeman (Advisor)
Jennifer McDonough (Committee Member)
Sean Veney (Committee Member)
Derek Damron (Committee Member)
Douglas Delahanty (Committee Member)
149 p.

Recommended Citations

Citations

  • Houston, S. A. (2014). Signal-Mediated Epigenetic Regulation of Oligodendrocyte Differentiation and Maturation via Alterations in Histone Acetylation Patterns: Implications for Multiple Sclerosis [Doctoral dissertation, Kent State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=kent1414756744

    APA Style (7th edition)

  • Houston, Sara. Signal-Mediated Epigenetic Regulation of Oligodendrocyte Differentiation and Maturation via Alterations in Histone Acetylation Patterns: Implications for Multiple Sclerosis. 2014. Kent State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=kent1414756744.

    MLA Style (8th edition)

  • Houston, Sara. "Signal-Mediated Epigenetic Regulation of Oligodendrocyte Differentiation and Maturation via Alterations in Histone Acetylation Patterns: Implications for Multiple Sclerosis." Doctoral dissertation, Kent State University, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=kent1414756744

    Chicago Manual of Style (17th edition)