Long-term maternal 2,3,7,8-Tetrachlorodibenzo-p-dioxin altered neuronal activities of brains of mouse offspring

长期母体2,3,7,8-四氯二苯并-对二恶英改变小鼠后代大脑的神经元活动

• 批准号: 13671019
• 负责人: NAGATOMO Itsugi
• 金额: $ 0.32万
• 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 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671019/
• 关键词: 2,3,7,8-Tetrachlorodibenzo-p-dioxin; dioxins; central nervous system; immunocytochemistry; Fos; 電気ショック

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is one of the most toxic environment contaminants. Acute administration of a lethal dose of TCDD to adult animals induces a variety of severe intoxication effects. Although penetration of TCDD into the brain is poor, it is still detected in the brain with higher concentrations in the hypothalamus. However, little direct morphological evidence clarifying whether the central nervous system (CNS) is involved in the TCDD-induced intoxication. Fos protein, a product of the immediate-early gene c-Fos, is generally considered to be a specific marker of neuronal activation. The present study was conducted to examine the c-Fos expression patterns in the CNS following administration of a single lethal dose of TCDD to the adult Long-Evans rat.On the other hand, TCDD is transferred to each fetus and pup transplacentally and lactationally, and it produces a wide variety of toxic effects in offspring. The CNS during early development may also be a potential target of TCDD. Previous study suggested that dopaminergic neurons of male non-human primates at least were targets of dioxin toxicity, and we examined serotonin-immunoreactive neurons in the raphe nuclei of male offspring of ddY mouse exposed to TCDD in utero and via lactation. Labeled neurons were similarly distributed in the raphe nuclei. However, a marked decrease in intensity of immunostaining occurred in all raphe nuclei, and consequently, the detectable serotonin-immunoreactive neurons were greatly decreased in number. The decreases in staining intensity occurred almost uniformly in each raphe subnucleus, the dorsal raphe nucleus, median raphe nucleus, supralemniscal area, nucleus raphe magnus.

2，3，7，8-四氯二苯并二恶英（TCDD）是一种毒性最大的环境污染物。对成年动物急性给予致死剂量的TCDD会引起各种严重的中毒效应。虽然TCDD渗透到大脑中的能力很差，但它仍然在大脑中检测到，下丘脑中的浓度较高。然而，很少有直接的形态学证据阐明中枢神经系统（CNS）是否参与了TCDD诱导的中毒。Fos蛋白是即早基因c-Fos的产物，通常被认为是神经元激活的特异性标志物。本研究的目的是探讨c-Fos的表达模式，在中枢神经系统管理后，一个单一的致死剂量的TCDD的成年Long-Evans大鼠。另一方面，TCDD转移到每个胎儿和幼鼠transplastently和lactationally，它产生了各种各样的毒性作用的后代。发育早期的中枢神经系统也可能是TCDD的潜在靶点。以往的研究表明，多巴胺能神经元的雄性非人类灵长类动物至少是二恶英毒性的目标，我们检查了ddY小鼠暴露于TCDD在子宫内和通过哺乳期的雄性后代中缝核中的多巴胺免疫反应阳性神经元。标记的神经元在中缝核团中也有类似的分布。然而，在所有中缝核的免疫染色强度发生显着下降，因此，可检测到的naphthonin免疫反应神经元的数量大大减少。在中缝各亚核、中缝背核、中缝正中核、梦系上区、中缝大核中，染色强度几乎一致地降低。

项目成果

Kuchiiwa S, et al.: "In Utero and Lactational exposure to 2,3,7,8-Tetrachlorodibenzo-p-dioxin decreases serotonin-immunoreactive neurons in raphe nuclei of male mouse offspring"Neurosci. Lett.. 317. 73-76 (2002)

Kuchiiwa S 等人：“在子宫内和哺乳期暴露于 2,3,7,8-四氯二苯并-对二恶英会降低雄性小鼠后代中缝核中的血清素免疫反应性神经元”Neurosci。

Kuchiiwa S, et al.: "In utero and lactional exposure to 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin decreases serotonin-immunoreactive neurons in raphe nuclei of male mouse offspring"Neurosci Lett. 317. 73-76 (2002)

Kuchiiwa S 等人：“在子宫内和哺乳期接触 2,3,7,8-四氯二苯并-对二恶英会降低雄性小鼠后代中缝核中的血清素免疫反应性神经元”Neurosci Lett。