The role of the prostaglandin E2 receptors in vulnerability of oligodendrocyte precursor cells to death
Open accessAbstract
BACKGROUND: Activity of cyclooxygenase 2 (COX-2) in mouse oligodendrocyte precursor cells (OPCs) modulates vulnerability to excitotoxic challenge. The mechanism by which COX-2 renders OPCs more sensitive to excitotoxicity is not known. In the present study, we examined the hypothesis that OPC excitotoxic death is augmented by COX-2-generated prostaglandin E2 (PGE2) acting on specific prostanoid receptors which could contribute to OPC death. METHODS: Dispersed OPC cultures prepared from mice brains were examined for expression of PGE2 receptors and the ability to generate PGE2 following activation of glutamate receptors with kainic acid (KA). OPC death in cultures was induced by either KA, 3'-O-(Benzoyl) benzoyl ATP (BzATP) (which stimulates the purinergic receptor P2X7), or TNFα, and the effects of EP3 receptor agonists and antagonists on OPC viability were examined. RESULTS: Stimulation of OPC cultures with KA resulted in nearly a twofold increase in PGE2. OPCs expressed all four PGE receptors (EP1-EP4) as indicated by immunofluorescence and Western blot analyses; however, EP3 was the most abundantly expressed. The EP3 receptor was identified as a candidate contributing to OPC excitotoxic death based on pharmacological evidence. Treatment of OPCs with an EP1/EP3 agonist 17 phenyl-trinor PGE2 reversed protection from a COX-2 inhibitor while inhibition of EP3 receptor protected OPCs from excitotoxicity. Inhibition with an EP1 antagonist had no effect on OPC excitotoxic death. Moreover, inhibition of EP3 was protective against toxic stimulation with KA, BzATP, or TNFα. CONCLUSION: Therefore, inhibitors of the EP3 receptor appear to enhance survival of OPCs following toxic challenge and may help facilitate remyelination.
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Inhibition of COX-2 has been confirmed to defend oligodendrocyte precursor cells under various damage conditions.
“inhibition of this enzyme has been confirmed to defend oligodendrocyte precursor cells under various damage conditions [159,160].”
From Beneficial Effects of Spirulina Consumption on Brain Health (2022) · cites this paper as [159]
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- Authors
- Carlson, N. G., Bellamkonda, S., Schmidt, L., Redd, J., Huecksteadt, T., Weber, L. M., Davis, E., Wood, B., Maruyama, T., & Rose, J. W.
- Affiliations
- University of Utah (US)
- VA Salt Lake City Healthcare System (US)
- Ono Pharmaceutical (Japan) (JP)
- Corresponding author
- Carlson, Noel G.
- Venue
- Journal of Neuroinflammation
- Published
- 2015-05-23
- Volume
- 12
- Issue
- 1
- Pages
- 101-101
- ISSN
- 1742-2094 (ISSN-L)
- PMC
- PMC4449524
- OpenAlex
- W1590240695
- Cited by
- 11
- References
- 38
- Citations by year
- 2026: 1 · 2025: 3 · 2023: 1 · 2022: 1 · 2021: 1 · 2018: 1 · 2017: 2 · 2016: 1
- FWCI
- 0.96
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Journal of Neuroinflammation (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Department of Veterans Affairs (Grant code:ID0EKTAE189, Grant code:ID0ELZAE190)
- Topics
- Health Sciences › Medicine › Pharmacology › Inflammatory mediators and NSAID effects
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Keywords
- oligodendrocyte precursor cells, prostaglandin E2, EP3 receptor, cyclooxygenase-2, excitotoxicity, cell death, kainic acid, P2X7 receptor, TNF-α, remyelination, neuroprotection, prostanoid receptors
- MeSH terms
- Adenosine Triphosphate, Animals, Cells, Cultured, Enzyme Inhibitors, Isoxazoles, Kainic Acid, Oligodendroglia, Stem Cells, Sulfones, Time Factors, Dinoprostone, Cell Death, Receptors, IgG, Receptors, Glutamate, Receptors, Prostaglandin E, Mice, Cyclooxygenase 2
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