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The effects of excitotoxicity and microglial activation on oligodendrocyte survival

Miller, Brandon Andrew
http://rave.ohiolink.edu/etdc/view?acc_num=osu1177537595

Abstract Details

2007, Doctor of Philosophy, Ohio State University, Neuroscience.
The nervous system transmits information over long distances by action potentials carried by neurons. In both the central and peripheral nervous system, neurons are insulated by myelin which improves the conduction of action potentials. In the peripheral nervous system, myelin is produced by Schwann cells. Oligodendrocytes (OLs) are the myelinating cells of the central nervous system (CNS). Both mature OLs and oligodendrocyte progenitor cells (OPCs) are lost in CNS disease and injury. Two contributing factors to OL and OPC cell death are inflammation and excitotoxicity. These studies were designed to better understand how OLs and OPCs respond to excitotoxicity and inflammatory stimuli. The glutamate receptor agonist kainic acid (KA) was used to induce excitotoxic cell death in OLs from optic nerve. We found that the pro-inflammatory cytokine tumor necrosis factor-alpha increased the susceptibility of optic nerve OLs to KA. Subsequent experiments tested the response of cortical OLs at different developmental stages to KA and revealed that mature cortical OLs were also vulnerable to KA-induced excitotoxicity. In the final set of experiments, we used combined culture of OLs or OPCs and microglia (MG) to study the effects of activated MG on OPC and OL survival. We found that MG activated with lipopolysaccharide induced OPC cell death, but MG, regardless of activation state, protected mature OLs from apoptotic cell death. We also observed that MG cell death occurs as a consequence of activation. Taken together, these studies demonstrate that both excitotoxicity and inflammatory stimuli can induce OL and OPC death but that MG can also support the survival of OLs.
Phillip Popovich (Advisor)
137 p.
oligodendrocyte; microglia; excitotoxicity; inflammation

Recommended Citations

Citations

  • Miller, B. A. (2007). The effects of excitotoxicity and microglial activation on oligodendrocyte survival [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1177537595

    APA Style (7th edition)

  • Miller, Brandon. The effects of excitotoxicity and microglial activation on oligodendrocyte survival. 2007. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1177537595.

    MLA Style (8th edition)

  • Miller, Brandon. "The effects of excitotoxicity and microglial activation on oligodendrocyte survival." Doctoral dissertation, Ohio State University, 2007. http://rave.ohiolink.edu/etdc/view?acc_num=osu1177537595

    Chicago Manual of Style (17th edition)

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© 2007, all rights reserved.
This open access ETD is published by The Ohio State University and OhioLINK.