Brain serotonin system disorder induced by in utero and lactational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin in rat.

大鼠在子宫内和哺乳期接触 2,3,7,8-四氯二苯并-对二恶英引起的脑血清素系统紊乱。

• 批准号: 13833006
• 负责人: KUCHIIWA Satoshi
• 金额: $ 2.11万
• 依托单位: Kagoshima University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13833006/
• 关键词: dioxin toxicity; serotonin immunoreactivity; enkephalin; immunohistochemistry; nitric oxide; neurotransmitter disorder; endocrine disruptor; encephalopathy; 神経伝達物質; 環境かく乱化学物質; 行動異常; 神経毒性; 神経化学的影響; 胎盤母乳暴露; 内分泌かくらん化学物質

1.Female ddY mice were administered 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) by gavage. In the breast-fed offspring born to the TCDD-exposed mice at 42 days of age, a marked decrease in intensity of serotonin immunostaining occurred in all raphe nuclei compared with the control offspring. In utero and/or lactational TODD exposure causes a long-lasting change in the serotonergic system in the raphe nuclei of offspring.2.After a single administration of TODD to the adult Long-Evans rat, a significantly large number of Fos-immunoreactive cells were found in the hypothalamus, amygdaloid nucleus and bed nucleus of the stria terminalis. It is suggested that these areas play an important role in TCDD-induced anorexia and progressive body weight loss.3.After a single administration of TCDD to the rats, neuronal nitric oxide synthase (nNOS) Western blotting experiment indicated marked decrease in nNOS immunoreactivity in the brain. NADPH-diaphorase histochemistry showed a marked decrease in the number of positive cells in the hypothalamus. The results suggest that TODD down-regulates nitric oxide product in the hypothalamus, which may be partially responsible for TODD-induced feeding inhibition.4.After TODD gastric administration to the rat, a marked increase in the density of methionine-enkephalin immunoreactive cell bodies, fibers and terminals was found in the forebrain. All these results suggest that some TODD toxicity may be induced by its direct action on the central nervous system.

1.给雌性ddy小鼠灌胃染毒2，3，7，8-四氯二苯并-对二恶英(TCDD)。在暴露于TCDD的小鼠42天出生的母乳喂养的后代中，与对照组相比，所有中缝核团中5-羟色胺免疫染色的强度都显著降低。2.成年Long-Evans大鼠一次给药后，在下丘脑、杏仁核和终纹床核可见大量Fos免疫反应阳性细胞。提示这些区域在TCDD引起的厌食和进行性体重减轻中起重要作用。3.TCDD单次给药后，神经元型一氧化氮合酶(NNOS)免疫印迹实验显示大鼠脑内nNOS免疫反应性明显降低。NADPH-黄递酶组织化学显示下丘脑阳性细胞数明显减少。结果提示，托德下调下丘脑一氧化氮产物，这可能是托德引起的摄食抑制的部分原因。4.托德灌胃后，大鼠前脑内甲硫氨酸脑啡肽免疫反应阳性细胞体、纤维和终末的密度明显增加。所有这些结果表明，托德的某些毒性可能是通过对中枢神经系统的直接作用而引起的。

项目成果

Cheng, S.-B, 他: "Dioxin exposure down-regulates nitric oxide synthase and NADPH-diaphorase activities in the hypothalamus of Long-Evans rat."Neuroscience Letters. 345. 5-8 (2003)

Cheng, S.-B 等人：“接触二恶英会下调 Long-Evans 大鼠下丘脑中的一氧化氮合酶和 NADPH-黄酶活性。”《神经科学快报》345. 5-8 (2003)。

Cheng, S.-B他: "Up-regulation of methionine-enkephalin-like immunoreactivity by 2,3,7,8-tetrachlorodibenzo-p-dioxin treatment in the forebrain of the rat."Journal of Chemical Neuroanatomy. 25. 73-82 (2003)

Cheng, S.-B 等人：“通过 2,3,7,8-四氯二苯并-对二恶英治疗大鼠前脑，上调甲硫氨酸-脑啡肽样免疫反应性。”《化学神经解剖学杂志》25。 73 -82 (2003)

Shi-Bin Cheng: "Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin treatment on methionine-enkephalin immunoreactivity in the brain of the Long-Evans rat."Organohalogen Compounds. 57. 407-409 (2002)

Shi-Bin Cheng：“2,3,7,8-四氯二苯并-对二恶英治疗对 Long-Evans 大鼠大脑中蛋氨酸-脑啡肽免疫反应性的影响。”有机卤素化合物。

Cheng, C-B.: "Up-regulation of methionine-enkephalin-like immunoreactivity by 2,3,7,8-tetrachlorodibenzo-p-dioxin treatment in the forebrain of the Long-Evans rat"Journal of Chemical Neuroanatomy. (In press).

Cheng，C-B.：“通过 2,3,7,8-四氯二苯并-对-二恶英治疗 Long-Evans 大鼠前脑，上调蛋氨酸-脑啡肽样免疫反应性”《化学神经解剖学杂志》。

口岩 聡: "ダイオキシンの胎盤・母乳暴露による脳異常"鹿児島学のプロフィール. 3. 21-26 (2001)

Satoshi Kuchiiwa：“胎盘和母乳接触二恶英导致的大脑异常”鹿儿岛科学概况（Kagoshima Science Profile）3. 21-26（2001）。