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The experimental study for the evaluation of the developmental neurotoxicity of tributyltin compounds

三丁基锡化合物发育神经毒性评价的实验研究

基本信息

批准号：
15590516
负责人：
TSUNODA Masashi
金额：
$ 2.3万
依托单位：
Kitasato University (2004-2005)Fukushima Medical University (2003)
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 2005
项目状态：
已结题

项目摘要

Pregnant ICR mice were exposed to TBT chloride at concentrations of 0, 15, or 50 ppm in water or 125 ppm in food. Male offspring were sacrificed at 1, 2 and 3 weeks after birth. The concentrations of norepinephrine, dopamine (DA), dihydoxyphenylacetic acid, homovanillic acid (HVA), serotonin (5-HT), and 5-hydroxyindolacetic acid (5-HIAA) were determined in different brain regions by HPLC. All offspring from the 125 ppm group died immediately after birth. A significant decrease in the body weight of the TBT-treated F1 groups compared to the control group was observed at the first week. Significant increases compared to the controls were observed for the DA concentration in the striatum of the 50 ppm F1 group, and for the HVA concentration in the cerebrum and the 5-HT concentration in the medulla oblongata of the 15 and 50 ppm F1 groups at the third week. At three weeks of age, the neurotransmitters and their metabolites may be useful indexes for developmental neurotoxicity. For the dams, a significant decrease in the 5-HT concentration was observed in the cerebellum, medulla, midbrain and striatum of the 125 ppm group compared to the control group. A significant decrease in the 5-HIAA concentration was also observed in the cerebellum, midbrain and striatum of the dams in the 125 ppm group compared to the control.In the same protocol, the [^3H]MK-801 binding level to N-methyl-D-aspartate (NMDA) receptors siginificantly decreased in the 15 ppm F1 group at 1 week and in the 15 ppm and 50 ppm F1 groups at 3 weeks of age, compared with that in the corresponding control F1 group.

怀孕的ICR小鼠暴露在浓度为0、15或50 ppm的水中或125 ppm的食物中。雄性子代分别于出生后1、2、3周处死。采用高效液相色谱法测定大鼠不同脑区去甲肾上腺素、多巴胺（DA）、二羟基苯基乙酸、高香草酸（HVA）、血清素（5-HT）、5-羟基吲哚乙酸（5-HIAA）的浓度。125 ppm组的所有后代在出生后立即死亡。与对照组相比，在第一周观察到tbt处理F1组的体重显著下降。与对照组相比，50 ppm F1组纹状体中DA浓度显著增加，15和50 ppm F1组第三周大脑中HVA浓度和延髓中5-羟色胺浓度显著增加。在三周龄时，神经递质及其代谢物可能是发育性神经毒性的有用指标。与对照组相比，125 ppm组的小脑、髓质、中脑和纹状体的5-HT浓度显著降低。与对照组相比，125 ppm组的小脑、中脑和纹状体的5-HIAA浓度也显著降低。在相同的方案中，与相应的对照F1组相比，15 ppm F1组在1周时和15 ppm和50 ppm F1组在3周龄时，MK-801与n -甲基- d -天冬氨酸（NMDA）受体的结合水平显著降低。