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

2，3，7，8-四氯二苯并对二恶英(TCDD)是毒性最大的环境污染物之一。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在大脑中的渗透性很差，但它仍然在大脑中被检测到，下丘脑的浓度较高。然而，几乎没有直接的形态学证据来阐明中枢神经系统(CNS)是否参与了TCDD诱导的中毒。Fos蛋白是即刻早期基因c-Fos的产物，通常被认为是神经元激活的特异性标志。本研究旨在研究成年Long-Evans大鼠单次注射致死剂量TCDD后中枢神经系统c-Fos的表达模式。另一方面，TCDD通过胎盘和哺乳期转移到每个胎儿和幼鼠体内，并对子代产生各种毒性效应。发育早期的中枢神经系统也可能是TCDD的潜在靶点。以前的研究表明，雄性非人灵长类动物的多巴胺能神经元至少是二恶英中毒的靶点，我们检测了宫内和哺乳期暴露于TCDD的雄性ddy小鼠后代中缝核中的5-羟色胺免疫反应神经元。标记神经元在中缝核团中也有类似的分布。然而，所有中缝核团的免疫染色强度都显著降低，因此，可检测到的5-羟色胺免疫反应神经元的数量大大减少。各亚核、中缝背核、中缝正中核、大脑中缝上区、中缝大核的染色强度降低几乎一致。

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.