Journal article
Reduced Extracellular Zinc Levels Facilitate Glutamate-Mediated Oligodendrocyte Death after Trauma
Journal of neuroscience research, v 91(6), pp 828-837
29 Mar 2013
PMID: 23553703
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Spinal cord injury results in irreversible paralysis, axonal injury, widespread oligodendrocyte death and white matter damage. While the mechanisms underlying this phenomenon are poorly understood, previous studies from our laboratory indicate inhibiting activation of the nuclear factor - κB transcription factor in astrocytes reduces white matter damage and improves functional recovery following spinal cord injury. In the current study, we demonstrate that activation of the nuclear factor - κB transcription factor within astrocytes results in a significant increase in oligodendrocyte death following trauma by reducing extracellular zinc levels and inducing glutamate excitotoxicity. Using an ionotropic glutamate receptor antagonist (CNQX), we show astroglial nuclear factor-κB-mediated oligodendrocyte death is dependent upon glutamate signaling despite no change in extracellular glutamate concentrations. Further analysis demonstrated a reduction in levels of extracellular zinc in astrocyte cultures with functional nuclear factor-κB signaling following trauma. Co-treatment of oligodendrocytes with glutamate and zinc showed a significant increase in oligodendrocyte toxicity in low zinc conditions, suggesting the presence of zinc at specific concentrations can prevent glutamate excitotoxicity. These studies demonstrate a novel role for zinc in regulating oligodendrocyte excitotoxicity and identify new therapeutic targets to prevent oligodendrocyte cell death in central nervous system trauma and disease.
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Details
- Title
- Reduced Extracellular Zinc Levels Facilitate Glutamate-Mediated Oligodendrocyte Death after Trauma
- Creators
- Joshua T. Johnstone - University of MiamiPaul D. Morton - University of MiamiArumugam R. Jayakumar - University of MiamiValerie Bracchi-Ricard - University of MiamiErik Runko - University of MiamiDaniel J. Liebl - University of MiamiMichael D. Norenberg - University of MiamiJohn R. Bethea - University of Miami
- Publication Details
- Journal of neuroscience research, v 91(6), pp 828-837
- Publisher
- Wiley
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biology; College of Arts and Sciences; Drexel University
- Web of Science ID
- WOS:000318047000009
- Scopus ID
- 2-s2.0-84876488157
- Other Identifier
- 991020099743604721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Neurosciences