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Effect of stress and nutrition on brain functions: Mechanism-based risk evaluation of combined exposure

压力和营养对脑功能的影响：基于机制的组合暴露风险评估

基本信息

批准号：
11557028
负责人：
WATANABE Chiho
金额：
$ 7.68万
依托单位：
The University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2001
项目状态：
已结题

项目摘要

One characteristic feature shared by most of the contemporary issues in the environmental health is that many causative agents are associated with a single health problem. In this study, attempts were made to develop an effective approach to evaluate the relative importance of each environmental agents in terms of human health risk. Brain dysfunctions were chosen as the target. As the models for the brain dysfunctions, hippocampal lesions induced by stresses and the striatum lesions induced by selenium (Se) deficiency. Moreover, the stress was combined with trimethyl tin (TMT), a chemical known to damage the hippocampus; on the other hand, the deficiency was combined with stress. As such interaction between a nutrient and a stress factor would be fully examined. In the hippocampal model, it was found that TMT-induced lesions were aggravated by adrenarectomy and alleviated by the administration of glucocorticoid, an observation contradict with the current belief. In the striatal model, it was shown for the first time that Se deficiency introduced after weaning is able to induce some behavioral anomaly. Although the openfield activity was reduced by the treatment with dexamethasone, there was no distinct interaction. In addition, a method was established to determine the extracellular concentrations of glutathione, a tripeptide responsible for the scavenge, in the striatum. This microdialysis technique revealed that hydrogen peroxide, an ROS generator, or desferal, a divalent iron chelator.

大多数当代环境卫生问题的一个共同特点是，许多病原体与单一的健康问题有关。在这项研究中，试图制定一种有效的方法来评估每一种环境因素对人类健康风险的相对重要性。脑功能障碍被选为目标。应激引起的海马损伤和硒缺乏引起的纹状体损伤作为脑功能障碍的模型。此外，压力与三甲基锡（TMT）结合在一起，这是一种已知会损害海马体的化学物质；另一方面，这种缺乏与压力结合在一起。因此，营养素和应激因素之间的相互作用将得到充分研究。在海马模型中，我们发现tmt引起的病变在肾上腺切除术后加重，在糖皮质激素的作用下减轻，这与目前的观点相矛盾。在纹状体模型中，首次显示断奶后引入的硒缺乏能够引起一些行为异常。虽然使用地塞米松治疗降低了空地活性，但没有明显的相互作用。此外，还建立了一种方法来测定纹状体中负责清道夫的三肽谷胱甘肽的细胞外浓度。这种微透析技术揭示了过氧化氢，一种ROS发生器，或desferal，一种二价铁螯合剂。