Shati/Nat8lを介した線条体BDNF制御による社会性ストレスに対する抵抗性の形成

• Published in: 日本薬理学会年会要旨集 p. 1-Y-F1-2
• Main Authors: 村松, 慎一, 新田, 淳美, 宮西, 肇
• Format: Journal Article
• Language: Japanese
• Published: 公益社団法人 日本薬理学会 2021
• Subjects: depression; stress
• ISSN: 2435-4953
• DOI: 10.1254/jpssuppl.94.0_1-Y-F1-2

[Background] In pathogenesis of depression, BDNF in the brain plays an important role. We found that Shati/Nat8l and BDNF mRNA levels were increased in the striatum of depression model mice exposed repeated social defeat stress (R-SDS), and they were corelated. In this study, we revealed the mechanism of regulation in BDNF by Shati/Nat8l and the roles of striatal BDNF in depression. [Methods] C57BL/6J male mice were exposed R-SDS using ICR mice, and the acetylated histone levels in BDNF promoter region in the striatum was measured using chromatin immunoprecipitation. We generated striatal Shati/Nat8l conditional knockdown mice (Shati cKD) using Cre-loxP system. Then, we assessed depression-like behaviors in Shati cKD after R-SDS. We investigated the role of striatal BDNF in depression using ANA-12, inhibitor of BDNF receptor (TrkB).[Results] Acetylated histone levels in BDNF promoter region in the striatum were increased in depression model mice. In the behavioral experiment, Shati cKD showed the resilience for social defeat stress. BDNF mRNA and acetylated histone levels of BDNF in the striatum were suppressed by knockdown of Shati/Nat8l. Mice exposed R-SDS with ANA-12 showed the resilience for social defeat stress.  [Conclusions] BDNF in the striatum regulates resilience for social defeat stress mediating histone acetylation by Shati/Nat8l. Our study suggested the novel mechanisms induced resilience for stress, and Shati/Nat8l and BDNF in the striatum could be a new target for medical tools for depression.