Analysis of Brain Function and Prevention of Brain Diseases focused on the Action of Trace Metals

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1. Enhanced glutamate exicitotoxicity in the hippocampus in zinc deficiencyGlutamate exitotoxicity is a final common pathway for numerous pathological processes such as Alzheimer's disease and amyotrophic lateral sclerosis, in addition to stroke/ischemia and temporal lobe epilepsy. Susceptibility to kainate-induced seizures was enhanced in zinc-deficient mice and rats. Glutamate exicitotoxicity is enhanced in the hippocampus in zinc deficiency2. Role of zinc in synaptic neurotransmission in the hippcampusZinc exists in high densities in the giant boutons of hippocampal mossy fibers. On the basis of the evidence that zinc decreases extracellular glutamate concentration in the hippocampus, the presynaptic action of zinc released from mossy fibers during tetanic stimulation was examined using hippocampal slices. Zinc released from mossy fibers is a negative-feedback factor against presynaptic activity during tetanic stimulation.3. Unique response of hippocampal zinc to Novelty StressTo analyze the response of extracellular zinc in the hippocampus against novelty stress, rats were placed for 50 min in a novel environment once a day for 8 days. Extracellular glutamate in the hippocampus was increased during exploratory behavior on day 1, whereas extracellular zinc was decreased. Extracellular zinc returned to the basal level during exploratory behavior on day 8. The decrease in extracellular zinc and the increase in extracellular glutamate in exploratory period were abolished by perfusion with CaEDTA, a membrane-impermeable zinc chelator.. These results suggest that zinc uptake by hippocampal cells is linked to exploratory activity and is required for the activation of glutamatergic neurotransmitter system.