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Brain neurotransmitter abnormalities and behavioral alterations induced by in utero exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin at secondary sexual characteristic stage of development.

第二性征发育阶段子宫内暴露于 2,3,7,8-四氯二苯并-对-二恶英引起的脑神经递质异常和行为改变。

基本信息

批准号：
15510062
负责人：
KUCHIIWA Toshiko
金额：
$ 2.18万
依托单位：
Kagoshima Immaculate Heart University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2006
项目状态：
已结题

项目摘要

1. We observed that perinatal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) caused enhanced hyperactive motor responses to soft touch simulation on the skin. We developed a new research instrument, Touch Response Meter, computing motor response activity of laboratory animals. The socially isolated depression model mice and the dioxin exposed depressed mice were tested in this instrument. We demonstrated that the screening of the depressed animals and quantitative estimating of degree of depression were computable using this new research instrument.2. Female ddY mice were administered TCDD by gavage and mated with normal male mice. The nose poke test was performed in their offspring to evaluate the effects of perinatal TCDD exposure on exploratory behavior at the secondary sexual characteristic and pubertal stages of development. The perinatal TCDD-exposed offspring at these stages showed decreased nose poke behavior, suggesting the perinatal TCDD exposure decrease exploratory behavior in these stages.3. Female pregnant mice were received oral administration of TCDD to evaluate the behavioral abnormalities of their offspring at the secondary sexual characteristic and pubertal stages of development. The male offspring showed hyperactive motor responses such as 'kicking off', 'escaping', 'attacking' and 'hiding' to mechanical soft stimulation on their skin. The behaviors continued from postnatal week 8 to 12 and more.4. Female pregnant mice were administered TCDD by gavage to evaluate the effect of perinatal TCDD exposure on the activity of the locus coeruleus of their offspring at the pubertal and young adult stages. A small number of immunopositive c-Fos neurons were observed in the nucleus in the high dosed TCDD-exposed offspring, but few positive cells were observed in the normal and low dosed offspring, indicating that the perinatal exposure of TCDD does not effect on the activity of the locus coeruleus of the male offspring at these stages.

1.我们观察到，围产期暴露于2，3，7，8-四氯二苯并-p-二恶英（TCDD）引起皮肤上的软触摸模拟增强多动运动反应。我们研制了一种新的研究仪器--触觉反应仪，用于计算实验动物的运动反应活动。用该仪器对社会隔离抑郁模型小鼠和二恶英暴露抑郁模型小鼠进行了测试。实验结果表明，抑郁动物的筛选和抑郁程度的定量评估是可计算的.雌性ddY小鼠通过灌胃给予TCDD，并与正常雄性小鼠交配。在其后代中进行鼻戳试验，以评估围产期TCDD暴露对第二性征和青春期发育阶段探索行为的影响。围产期TCDD暴露的子代在这两个阶段的戳鼻行为减少，提示围产期TCDD暴露在这两个阶段的探索行为减少.雌性孕鼠经口给予TCDD，以评估其子代在第二性征和青春期发育阶段的行为异常。雄性后代对皮肤上的机械性软刺激表现出过度活跃的运动反应，如“踢腿”、“逃跑”、“攻击”和“躲藏”。这些行为从出生后第8周到第12周甚至更长时间持续存在.通过灌胃给雌性妊娠小鼠施用TCDD，以评估围产期TCDD暴露对其子代青春期和青年期蓝斑活动的影响。在高剂量TCDD暴露的后代中，在细胞核中观察到少量免疫阳性c-Fos神经元，但在正常和低剂量后代中观察到很少的阳性细胞，表明围产期TCDD暴露对这些阶段的雄性后代蓝斑的活动没有影响。