マウスの社会挫折ストレスによる脳内のプロスタグランジンE2産生のメカニズムとその役割

• Published in: 日本薬理学会年会要旨集 p. 1-YIA-05
• Main Authors: 聶, 翔, 北岡, 志保, 古屋敷, 智之
• Format: Journal Article
• Language: Japanese
• Published: 公益社団法人 日本薬理学会 2020
• Subjects: arachidonic acid; cannabinoid; prostaglandin; stress
• ISSN: 2435-4953
• DOI: 10.1254/jpssuppl.93.0_1-YIA-05

Prolonged or excessive stress caused by social environment induces psychological and physiological alterations, and increases a risk for psychiatric disorders. In repeated social defeat stress (SDS), a rodent model to study psychiatric disorders, we previously reported that prostaglandin (PG) E2, an inflammation-related lipid mediator, and toll-like receptor (TLR) 2/4, innate immune receptors, are crucial for repeated SDS-induced social avoidance. However, the mechanism of SDS-induced PGE2 synthesis in the brain and the involvement of TLR2/4 remain unknown. Here we show that SDS increased the PGE2 contents in subcortical brain regions of wild-type mice, and that this increase was abolished by perturbations of TLR2/4, COX1 and COX2. It has been reported that free arachidonic acid for PGE2 synthesis in the brain is supplied from monoacylglycerol lipase (MAGL)-mediated metabolism of endocannabinoid 2-arachidonoylglycerol. Consistently, systemic administration of JZL184, a MAGL inhibitor, inhibited SDS-induced PGE2 synthesis in subcortical regions and social avoidance. These results suggest that SDS induces PGE2 synthesis derived from 2-arachidonoylglycerol via the MAGL-COX pathway in subcortical regions to induce social avoidance, and that this PGE2 synthesis is maintained by TLR2/4 activity.