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

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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.