WANIAR4 ( M) Development of the animal model for postpartum psychosis and the elucidation of pathogenic mechanisms through estrogen action

WALIAR4 (M) 产后精神病动物模型的开发以及通过雌激素作用阐明致病机制

• 批准号: 20790198
• 负责人: NAGATANI Miyako
• 金额: $ 2.75万
• 依托单位: St.Marianna University School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2009
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20790198/
• 关键词: 生殖生理学; 産後精神病; 母ラット; エストロジェン; 不安様行動; うつ様行動; ERα; ERβ; 出産

We found that primiparous rats at 3 weeks-postpartum showed increased anxiety and depressive behaviors in elevated plus maze (EP) and forced swimming (FS) tests, compared with diestrus nulliparous females. ERa-selective agonist and estrogen displayed anxiolytic and antidepressant effects in EP and FS tests at 3 weeks-postpartum after subcutaneous injection once daily for 4 days. Furthermore, we found a marked alteration in the expression of TrkB and BDNF (brain-derived neurotrophic factor) receptors, and in resultant intracellular signaling of the 3 weeks-postpartums. This raises a possibility that changes of neurotrophin signaling via ERa stimulation are associated with anxiety and depression-like behaviors. In couclusion, we identified an animal model of postpartum psychosis and postpartum depression, which could be employed to develop innovative drugs of ERa stimulant for these diseases.

我们发现，与间情未孕雌性大鼠相比，产后3周的未孕大鼠在高架十字迷宫（EP）和强迫游泳（FS）测试中表现出增加的焦虑和抑郁行为。雌激素选择性激动剂和雌激素在产后3周的EP和FS试验中显示出抗焦虑和抗抑郁作用，每天皮下注射一次，持续4天。此外，我们发现了一个显着的变化，TrkB和BDNF（脑源性神经营养因子）受体的表达，并在所产生的细胞内信号的3周postpartums。这提出了一种可能性，即通过ER α刺激的神经营养因子信号传导的变化与焦虑和抑郁样行为相关。结论：建立了产后精神病和产后抑郁症的动物模型，可用于开发ER α激动剂的创新药物。

项目成果

Possible anxiolytic effect of quazepam in the daytime: behavioral analysis in mice

夸西泮在白天可能的抗焦虑作用：小鼠行为分析

• 发表时间: 2008
• 作者: Izumi A;Kajiyama Y;Furuta M;Shiosaka S;Kunugi H
• 通讯作者: Kunugi H

プレドニゾロンによるマウスの行動変化

泼尼松龙诱导小鼠行为改变

• 发表时间: 2008
• 作者: 梶山優;古田都;二宮碧;柴田重信;功刀浩
• 通讯作者: 功刀浩

Possible anxiolytic effect of quazepam in the daytime : behavioral analysis in mice

夸西泮在白天可能的抗焦虑作用：小鼠行为分析

• 发表时间: 2008
• 作者: Izumi A;Kajiyama Y;Furuta M;Shiosaka S;Kunugi H;Izumi A(他4名)
• 通讯作者: Izumi A(他4名)

Biomarkers for Psychiatric Disorders(A Brief Overview, Turck (ed. ), Animal Models for Schizophrenia, Chapter 7)

精神疾病的生物标志物（简要概述，图尔克（编辑），精神分裂症动物模型，第 7 章）

• 发表时间: 2008
• 作者: Furuta M;Kunugi H
• 通讯作者: Kunugi H

Anxiolytic and antidepressant effects of estrogen through estrogen receptor a, but notβ, in postpartum rats after weaning pups

雌激素通过雌激素受体 a 而不是 β 对断奶后产后大鼠的抗焦虑和抗抑郁作用

• 发表时间: 2009
• 作者: Furuta M;Ninomiya M;Chiba S;Kajiyama Y;Shibata S;Akema T;Kunugi H
• 通讯作者: Kunugi H