| Project/Area Number |
16390035
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Environmental pharmacy
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| Research Institution | University of Shizuoka |
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Principal Investigator |
TAKEDA Atsushi University of Shizuoka, Department of Medical Biochemistry, Associate Professor, 薬学部, 助教授 (90145714)
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| Project Period (FY) |
2004 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥13,800,000 (Direct Cost: ¥13,800,000)
Fiscal Year 2006: ¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2005: ¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2004: ¥6,500,000 (Direct Cost: ¥6,500,000)
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| Keywords | zinc / hippocampus / glutamate / zinc-deficient diet / synaptic neurotransmission / glutamate excitotoxicity / calcium / essential trace metal / 精神的ストレス / 新規環境 / 生体微量金属 / 神経伝達調節因子 / 亜鉛不足 / てんかん |
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| Research Abstract |
1. Enhanced glutamate exicitotoxicity in the hippocampus in zinc deficiency
Glutamate 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 deficiency
2. Role of zinc in synaptic neurotransmission in the hippcampus
Zinc 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 Stress
To 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.
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