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Prostaglandin E2 in Oxidopamine-induced Neuronal Inflammation and Injury

Kang, Xu
http://orcid.org/0000-0002-1957-6910
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1491318171029971

Abstract Details

2017, MS, University of Cincinnati, Pharmacy: Pharmaceutical Sciences.
Cyclooxygenase-2 (COX-2) is upregulated in many neurological conditions including strokes, epilepsies, neurodegenerative diseases, brain tumors, etc., and plays a pivot role in promoting inflammatory processes within the brain that might facilitate neuronal degeneration and functional impairments. Mounting evidence from preclinical and clinical studies suggests that the pro-inflammatory actions of COX-2 are largely attributed to its major prostanoid product – prostaglandin E2 (PGE2). PGE2 is involved in a variety of physiological and pathological proceedings in the central nervous system (CNS) via activating four G-protein coupled receptors (GPCRs) – EP1, EP2, EP3 and EP4. However, which EP receptor is the culprit of PGE2-mediated neuroinflammation and neurodegeneration remains largely unclear and is presumably dependent on the brain insult types and the responding molecular and cellular components. Here, we show evidence that the COX-2, PGE2 and pro-inflammatory cytokine interlukine-1ß (IL-1ß) are substantially induced in neuronal cells – Neuro-2a (mouse) and SH-SY5Y (human) – that are treated with neurotoxin 6-hydroxydopamine (6-OHDA). Taking advantage of our recently developed novel selective EP2 antagonists – TG4-155 and TG6-10-1, we further demonstrate that EP2 receptor is the major Gas-coupled receptor that mediates PGE2-initiated cAMP-dependent signaling pathway in Neuro-2a and SH-SY5Y cells, and largely contributes to 6-OHDA-induced neurotoxicity. Furthermore, microinjection of 6-OHDA into the striatum also causes COX-2 induction in the brain followed by the upregulation of many inflammation and gliosis-associated genes such as IL-1ß, TNF-a, Iba-1 and GFAP in Sprague Dawley rats. Our results suggest that pharmacological inhibition of EP2 receptor might represent a novel strategy to prevent brain inflammation and injury in neurodegenerative diseases such as Parkinson’s disease.
Jianxiong| Jiang, Ph.D. (Committee Chair)
Gary| Gudelsky|, Ph.D. (Committee Member)
Jiukuan Hao|, Ph.D. (Committee Member)
45 p.
Pharmaceuticals
PGE2; EP2; PD; COX-2; Neuroinflammation; 6-OHDA

Recommended Citations

Citations

  • Kang, X. (2017). Prostaglandin E2 in Oxidopamine-induced Neuronal Inflammation and Injury [Master's thesis, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1491318171029971

    APA Style (7th edition)

  • Kang, Xu. Prostaglandin E2 in Oxidopamine-induced Neuronal Inflammation and Injury. 2017. University of Cincinnati, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1491318171029971.

    MLA Style (8th edition)

  • Kang, Xu. "Prostaglandin E2 in Oxidopamine-induced Neuronal Inflammation and Injury." Master's thesis, University of Cincinnati, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1491318171029971

    Chicago Manual of Style (17th edition)

ucin1491318171029971
156
© 2017, all rights reserved.
This open access ETD is published by University of Cincinnati and OhioLINK.