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Updated: Mar 7, 2026
Modeling Neuronal Death and Degeneration in Mouse Primary Cerebellar Granule Neurons
Published on: November 6, 2017
Excitotoxicity-induced prostaglandin D2 production induces sustained microglial activation and delayed neuronal death
Kensuke Iwasa1, Shinji Yamamoto1, Sosuke Yagishita1
1Department of Pharmacology, Faculty of Medicine, Saitama Medical University, Iruma-gun, Saitama, Japan.
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 PGF2α 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 PGF2α in rats whose hippocampal PG productions were entirely blocked by pretreatment of NS398, a COX-2 selective inhibitor. Administration of PGD2 and PGF2α 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.
Insights
Prostaglandin D2 (PGD2) and Prostaglandin F2α (PGF2α) contribute to delayed neuronal death after excitotoxicity. PGD2 specifically activates microglia, suggesting a role in this process.
Area of Science:
- Neuroscience
- Neuroinflammation
- Neurodegeneration
Background:
- Excitotoxicity is a key mechanism in neuronal death, with prostaglandins (PGs) playing a significant role in neurodegenerative diseases.
- Cyclooxygenase-2 (COX-2) produces PGD2, PGE2, and PGF2α during excitotoxicity in the hippocampus.
- Blocking all PG production previously ameliorated hippocampal neuronal death following kainic acid (KA) administration.
Purpose of the Study:
- To investigate the specific roles of individual PGs (PGD2, PGE2, PGF2α) in delayed hippocampal neuronal death.
- To determine the contribution of PGD2 to microglial activation in the context of excitotoxicity.
Main Methods:
- Rats received intracerebroventricular injections of PGD2, PGE2, or PGF2α after hippocampal PG production was blocked by the COX-2 inhibitor NS398.
- Delayed neuronal death was assessed 30 days after a single systemic kainic acid (KA) administration.
Main Results:
- Both PGD2 and PGF2α demonstrated a latent contribution to delayed neuronal death, persisting for 30 days post-KA treatment.
- PGD2 administration was found to enhance microglial activation in the hippocampus.
Conclusions:
- Excitotoxic delayed neuronal death is influenced by PGD2 and PGF2α.
- PGD2-induced microglial activation is implicated as a potential mediator of delayed neuronal death in the hippocampus.
