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J Lipid Res. 2017 Apr;58(4):649-655. doi: 10.1194/jlr.M070532. Epub 2017 Feb 7.

Excitotoxicity-induced prostaglandin D2 production induces sustained microglial activation and delayed neuronal death.

Author information

1
Department of Pharmacology, Faculty of Medicine, Saitama Medical University, Iruma-gun, Saitama, Japan.
2
Department of Pharmacology, Faculty of Medicine, Saitama Medical University, Iruma-gun, Saitama, Japan keisukey@saitama-med.ac.jp.

Abstract

Excitotoxicity is the pivotal mechanism of neuronal death. Prostaglandins (PGs) produced during excitotoxicity play important roles in neurodegenerative conditions. Previously, we demonstrated that initial burst productions of PGD2, PGE2, and PGF are produced by cyclooxygenase-2 (COX-2) in the hippocampus following a single systemic kainic acid (KA) administration. In addition, we showed that blocking of all PG productions ameliorated hippocampal delayed neuronal death at 30 days after KA administration. To investigate the role of individual PGs in the delayed neuronal death, we performed intracerebroventricular injection of PGD2, PGE2, or PGF in rats whose hippocampal PG productions were entirely blocked by pretreatment of NS398, a COX-2 selective inhibitor. Administration of PGD2 and PGF had a latent contribution to the delayed neuronal death, sustained over 30 days after a single KA treatment. Furthermore, PGD2 enhanced microglial activation, which may be involved in the delayed neuronal death in the hippocampus. These findings suggest that excitotoxic delayed neuronal death is mediated through microglia activated by PGD2.

KEYWORDS:

kainic acid; microglia; neurons

PMID:
28174214
PMCID:
PMC5392741
DOI:
10.1194/jlr.M070532
[Indexed for MEDLINE]
Free PMC Article

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