What kind of neural circuit in the brain of prenatally stressed offspring may be responsible to the vulnerabill to chronic stress in adulthood

产前应激后代大脑中的哪种神经回路可能导致其成年后容易遭受慢性应激

• 批准号: 09670975
• 负责人: MIKUNI Masahiko
• 金额: $ 2.05万
• 依托单位: Gunma University School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09670975/
• 关键词: prenaral stress; animal model; vulnerability; neuronal plasiticity; septum; hypothalomo-pituitary-adrenal axis

It has been suggested that early adverse life events including childhood abuse, neglect, and parental loss may predispose individuals for the development of affective disorders in response to extreme stress exposure in adulthood. Recently, we have demonstrated that the prenatal saline injection stress produced an enhanced adrenocortical response to conditioned fear stress and a prolonged immobility duration in forced swimming stress, indicating that the prenatally stressed offspring seemed to be susceptive to an acute stress in adulthood endocrinologically and behaviorally. It is still unclear whether prenatally stressed rats can habituate to chronic stress in adulthood. We have investigated the stress response of c-fos mRNA expression in brain and of corticosterone secretion in prenatally stressed adult male rats during 14 days repeated restraint stress. To an acute restraint stress, prenatally stressed rats showed significantly increased response of c-fos mRNA expression, to the same extent, compared to control rats, in brain regions including para-ventricular nucleus, amygdala, locus ceruleus, raphe nucleus, cingulate cortex, piriform cortex, and seputum. Repeated restraint stress for 14 days induced significant reduction of c-fos response, compared to the expession of c-fos mRNA during acute restraint stress, in all investigated brain regions except septum of prenatally stressed rats. In septum, prenatally stressed rats showed significant increase in c-fos expression in response to repeated restraint stress, compared to control rats. In addition, control rats showed reduction of plasma corticosterone level at 120min after the beginning of restraint stress from the 7th day of stress, whereas prenatally stressed rats did not show such habituation. These findings indicate that the neural circuit including septum may be responsible to the vulnerabillty of prenatally stressed rats to chronic stress in adulthood.

有人认为，包括童年虐待、忽视和父母丧失在内的早期不良生活事件，可能使个人在成年后因极端压力暴露而易患上情感障碍。最近，我们已经证明，产前注射生理盐水应激能增强肾上腺皮质对条件恐惧应激的反应，并延长强迫游泳应激的不动持续时间，这表明产前应激子代似乎对成年后的急性应激有内分泌和行为上的易感性。目前尚不清楚产前应激大鼠是否能在成年后习惯于慢性应激。我们研究了14天重复束缚应激对孕期应激成年雄性大鼠脑内c-fos基因表达和皮质酮分泌的应激反应。与对照组相比，胎儿期应激大鼠在脑室旁核、杏仁核、蓝斑、中缝核、扣带回、梨状皮质和等脑区的c-fos基因表达显著增加。与急性束缚应激相比，重复束缚应激14天后，除隔区外，其余各脑区c-fos反应均显著降低。在隔区，与对照组相比，胎儿期应激大鼠对反复束缚应激的反应显示c-fos表达显著增加。此外，对照组大鼠在束缚应激开始后120min血浆皮质酮水平从应激第7天开始下降，而产前应激大鼠没有表现出这种习惯性。这些发现表明，包括隔区在内的神经回路可能与产前应激大鼠在成年期对慢性应激的脆弱性有关。

项目成果

三国 雅彦: "発達期のストレスと神経系の可塑性並びに感情障害脆弱性" 医事新報. 3815. 105 (1997)

三国正彦：“发育压力、神经系统可塑性和情绪障碍脆弱性”Iji Shinpo 3815. 105 (1997)。

Tomio Inoue, Takashi Shibasaki, Noboru Oriuchi, Keiko Aoyagi, Katsumi Tomiyoshi, Shigeko Amano, Masahiko Mikuni, Itsuro Ida, Jun Aoki, and Keigo Endo: "F-18 alpha-methyl tyrosine PET studies in patients with brain tumors." J.Nuclear Medicine. 40. 418-421

Tomio Inoue、Takashi Shibasaki、Noboru Oriuchi、Keiko Aoyagi、Katsumi Tomiyoshi、Shigeko Amano、Masahiko Mikuni、Itsuro Ida、Jun Aoki 和 Keigo Endo：“脑肿瘤患者的 F-18 α-甲基酪氨酸 PET 研究。”

三国 雅彦: "「胎生期ストレスによる神経の発達に伴う可塑的変化と感情障害病態モデル」感情機能と神経・免疫・内分泌-脳の世紀に向けて" 山脇成人編、親興医学出版社、東京、, 55-67 (1997)

三国正彦：“产前应激导致的神经发育相关的塑性变化和情感障碍的病理模型”情绪功能和神经、免疫和内分泌学 - 迈向大脑的世纪，山胁正人编辑，大矢子医学出版社，有限公司，东京；55-67（1997）

三國雅彦、高橋清久編: "生体リズムと精神疾患" 学会出版センター, 236 (1997)

三国正彦、高桥清久（编）：《生物节律与精神障碍》学会出版中心，236（1997）

三國雅彦: "感情障害における神経発達学的側面" 脳の科学. 20. 767-773 (1998)

Masahiko Mikuni：“情绪障碍的神经发育方面”《脑科学》20. 767-773 (1998)。