Microdialytic and behavioral pharmacological evaluation of mice offspring prenatally exposed to low-level methylmercury.

对产前暴露于低水平甲基汞的小鼠后代进行微透析和行为药理学评估。

• 批准号: 08457124
• 负责人: SATOH Hiroshi
• 金额: $ 5.12万
• 依托单位: TOHOKU UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08457124/
• 关键词: methylmercury; trans-generation effects; behavioral effects; activity; learning; motor performance; selenium; mice; 胎生期曝露; 神経伝達物質; ドパミン; マウス; オープンフィールド試験; 放射状迷路試験; ビーム・バランス試験; ノルエピネフリン

This study aims at providing basic information for the risk evaluation of human populations with long-term, low-level exposure to methylmercury. Emphasis was on the latent effects of prenatal exposure. Thus, the neurobehavioral effects of prenatal methylmercury exposure were evaluated in mice, focusing on the differential susceptibility among various behavioral functions. Pregnant ICR mice were injected with 0.3-1 mgHg/kg/day of methylmercury from day 10 to 18 of gestation. The behavioral function of the offspring was evaluated by open-field test, radial maze, and balance beam from Weaning to approx. 10 months age. Function of glutamatergic system in the hippocampus was evaluated by microdialysis In addition, modification of the neurotoxicity of methyhnercury by selenium nutrition and heat as confounding factors was also examined.The results obtained in this study can be summarized as follows :1) the open-field test, often used as a test for activity level and emotionality, was proved … More to be a sensitive and reproducible technique to evaluate the effect of prenatal methylmercury, and superior to the radial maze or the balance-beam test. It is necessary to identify a human equivalent for this test through further behavioral and/or neurochemical analysis. On the other hand, it is also necessary to refine and improve the technique for evaluation of learning and motor functions.2) the microdialysis study showed that the hippocampal glutamatergic system responded to the prenatal methylmercury exposure. Considering that the exposure level was low and that the microdialytic evaluation was done at 10 month of age which was remote from the cessation of the exposure, the glutamatergic system may be a sensitive target for prenatal methylmercury.3) two possible underlying mechanism for the neurotoxicity of prenatal methylmercury, namely oxidative stress and imbalance of the thyroid hormone in fetal brain was also evaluated. Both of them appeared to be responsible to some extent and further studies. Less

本研究旨在为长期、低水平接触甲基汞的人群的风险评估提供基本信息。重点是产前暴露的潜在影响。因此，产前甲基汞暴露的神经行为的影响进行了评估，在小鼠中，侧重于不同的行为功能之间的敏感性差异。从怀孕第10天到第18天，向怀孕的ICR小鼠注射0.3 - 1毫克汞/千克/天的甲基汞。采用旷场实验、放射状迷宫和平衡木等方法对仔鼠的行为功能进行评价。十个月大。用微透析技术研究了海马神经元能系统的功能，并探讨了硒营养和热作为混杂因素对甲基神经元毒性的影响，结果表明：1）旷场实验证实了常用于活动水平和情绪性的实验 ...更多信息 是一种灵敏、重复性好的评价产前甲基汞效应的方法，优于放射状迷宫或平衡束试验。有必要通过进一步的行为和/或神经化学分析确定该试验的人体等效物。另一方面，学习和运动功能的评价技术也需要进一步完善和改进。2）微透析研究表明，海马神经元能系统对产前甲基汞暴露有反应。考虑到暴露水平较低，并且在10月龄时进行了微透析评估，这与停止暴露的时间相距甚远，因此，脑能系统可能是产前甲基汞的敏感靶点。3）还评估了产前甲基汞神经毒性的两种可能的潜在机制，即氧化应激和胎儿脑中甲状腺激素的失衡。他们两人似乎都在一定程度上负有责任，需要进一步研究。少

项目成果

渡辺・吉田・小山・笠沼・佐藤: "マウス胎児期におけるメチル水銀曝露が母体胎児系Se含有酵素の活性に及ぼす影響" Biomed Research an Trace Elewouts. 8. 199-200 (1997)

Watanabe、Yoshida、Koyama、Kasanuma 和 Sato：“胎儿甲基汞暴露对母胎含硒酶活性的影响”Biomed Research 和 Trace Elewouts（1997 年）。

Watanabe C.et al.: "In utero exposure to methylmercury and Se deficiency converge on the neruobehavioral outcome in mice" Neurotoxicology and Teratology. in press. (1999)

Watanabe C.等人：“在子宫内暴露于甲基汞和硒缺乏会影响小鼠的神经行为结果”《神经毒理学和畸胎学》。

Watanabe C.et al.: "Deficiency of selenium enhances the K^+-induced release of dopamine in the striatum of mice" Neuroscience Letters. 236. 49-52 (1997)

Watanabe C.等人：“硒的缺乏增强了小鼠纹状体中K 2 诱导的多巴胺的释放”《神经科学快报》。

Watanabe, C., K.Yoshida, Y.Kasanuma and H.Satoh: "In utero methylmercury exposure differentially affects the activities of selenoenzymes in the fetal mouse brain" Environmental Research. (in press). (1999)

Watanabe, C.、K.Yoshida、Y.Kasanuma 和 H.Satoh：“子宫内甲基汞暴露对胎儿小鼠大脑中硒酶的活性有不同影响”环境研究。

Watanabe, C., Y.Kasanuma, Y.Dejima and H.Satoh: "The effect of prenatal methylmercury exposure on the GSH level and lipid peroxidation in the fetal brain and placenta of mice" Tohoku Journal of Experimental Medicine. 187. 121-126 (1999)

Watanabe, C.、Y.Kasanuma、Y.Dejima 和 H.Satoh：“产前甲基汞暴露对小鼠胎儿大脑和胎盘中 GSH 水平和脂质过氧化的影响”东北实验医学杂志。