Strategies for the study of the disinhibition of Hypothalamic-Pituitary-Adrenal axis in affective disorders, using prenatal stress model.

使用产前应激模型研究情感障碍中下丘脑-垂体-肾上腺轴去抑制的策略。

• 批准号: 06670994
• 负责人: MIKUNI Masahiko
• 金额: $ 1.41万
• 依托单位: Department of Neuropsychiatry, Gunma University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06670994/
• 关键词: prenatal stress; neuronal plasiticity; hypothalamo-pituitary-adrenal axis; ストレス脆弱性; 強制水泳試験; グルココルチコイド受容体; 最初期遺伝子; コルチコトロピン遊離促進ホルモン遺伝子

In this study we have investigated whether animals prenatally exposed to mild stress produce the overactivity of Hypothalamo-Pituitary-Adrenal (HPA) axis and alterations of anxiety-or mood-related behaviors in the response to stressful stimuli as well as a deficit of monoaminergic activities in adult offspring, which are frequently seen in depression. The prenatal saline injection stress increased the corticosterone secretion to a significantly greater extent during conditioned fear stress in offspring at 7 and 28 weeks of age in comparison with controls. In addition, decreased entry numbers into open and closed arms in elevated plus maze for the first 5-min session were observed in the prenatally stressed groups, suggesting that prenatally stressed offspring were more anxious under the new environmental conditions than controls. A prolonged immobility duration in forced swimming test was also observed in the prenatally stressed adult offspring, indicating that the prenatally stressed offspring seemed to be susceptible to behavioral'despair'. On the other hand, the 5-hydroxytryptamine concentration in the hypothalamus from prenatally stressed offspring in adulthood was observed to be higher than controls, in contrast of unaltered serotonin metabolite, 5-hydroxyindoleacetic acid. This deficit of serotonergic activity may be one of the vulnerability factors, revealing overactivity of the HPA axis in the response to stressful stimuli. These results of endocrine response and altered behavioral activity under stressful conditions, and the deficit of serotonergic activity suggest that the prenatal saline injection stress model may have a face validity as an animal model of depression.

在这项研究中，我们已经调查了动物产前暴露于轻度应激是否产生过度活跃的下丘脑-垂体-肾上腺（HPA）轴和改变焦虑或情绪相关的行为在应激刺激的反应，以及赤字的单胺能活动在成年后代，这是常见的抑郁症。产前生理盐水注射压力增加皮质酮分泌到一个显着更大的程度上在条件性恐惧压力的后代在7和28周龄与对照组相比。此外，在产前应激组中观察到，在前5分钟的高架十字迷宫中，进入张开臂和闭合臂的数量减少，这表明产前应激的后代在新的环境条件下比对照组更加焦虑。在强迫游泳试验中，产前应激的成年子代也观察到了延长的不动时间，表明产前应激的子代似乎更容易出现行为“绝望”。另一方面，5-羟色胺浓度在下丘脑从产前强调后代在成年期被观察到高于对照组，在未改变的5-羟色胺代谢产物，5-羟吲哚乙酸的对比。这种多巴胺能活动的缺陷可能是脆弱性因素之一，揭示了HPA轴在应激刺激反应中的过度活动。这些结果的内分泌反应和改变的行为活动在压力条件下，和赤字的肾上腺素能活动表明，产前生理盐水注射应激模型可能有一个表面效度作为抑郁症的动物模型。

项目成果

三国雅彦: "発達障害医学の進歩 No. 6、有馬正高、熊谷公明、原 仁編" 診断と治療社, 89 (1994)

三国正彦：“发育障碍医学进展第 6 期，由有马正孝、熊谷公明和原仁编辑”诊断和治疗出版，89（1994）

K. Saitoh, M. Mikuni, et al: "Serotonin-induced 5-HT-1A receptor desensitization" Neuroscience Letters. 199. 191-194 (1995)

K. Saitoh、M. Mikuni 等人：“血清素诱导的 5-HT-1A 受体脱敏”神经科学快报。

Tetsuo Ogawa, Masahiko Mikuni, Yasukazu Kuroda, Katsumasa Muneoka, Kazuhiro John Mori and Kiyohisa Takahashi: "Periodic maternal deprivation alters stress response in adult offspring : Potentiates the negative feedback regulation of restraint stress-induc

Tetsuo Okawa、Masahiko Mikuni、Yasukazu Kuroda、Katsumasa Muneoka、Kazuhiro John Mori 和 Kiyohisa Takahashi：“周期性母性剥夺会改变成年后代的应激反应：增强约束应激诱发的负反馈调节

Ariyuki Kagaya, Masahiko Mikuni, Y Okamoto, Shin-ichiro Muraoka, Nobumasa Motohashi, Shigeto Yamawaki and Kiyohisa Takahashi: "W-7 facilitates 5-HT-2A receptor-mediated intracellular calcium increase in human platelets." Pharmaceutical Science. 1. 141-143

Ariyuki Kagaya、Masahiko Mikuni、Y Okamoto、Shin-ichiro Muraoka、Nobumasa Motohashi、Shigeto Yamawaki 和 Kiyohisa Takahashi：“W-7 促进 5-HT-2A 受体介导的人血小板细胞内钙增加。”

T. Ogawa, M. Mikuni, et al.: "Periodic maternal deprivatiom alters stress response in adult offspring" Pharmacol. Biochem. & Behav.49. 961-967 (1994)

T. Okawa、M. Mikuni 等人：“周期性母体剥夺会改变成年后代的应激反应” Pharmacol。