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标题：Age-Dependent Modification of Intracellular Zn2+ Buffering in the Hippocampus and Its Impact
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作者：Haruna Tamano ; Atsushi Takeda
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2019
卷号：42
期号：7
页码：1070-1075
DOI：10.1248/bpb.b18-00631
出版社：The Pharmaceutical Society of Japan
摘要：The basal concentrations of extracellular Zn2+ and intracellular Zn2+, which are approximately 10 nM and 100 pM, respectively, in the brain, are markedly lower than those of extracellular Ca2+ (1.3 mM) and intracellular Ca2+ (100 nM), respectively, resulting in much less attention paid to Zn2+ than to Ca2+. However, intracellular Zn2+ dysregulation, which is closely linked with glutamate- and amyloid β-mediated extracellular Zn2+ influx, is more critical for cognitive decline and neurodegeneration than intracellular Ca2+ dysregulation. It is estimated that the age-dependent increase in the basal concentration of extracellular Zn2+ in the hippocampus plays a key role in cognitive decline and neurodegeneration. The characteristics of extracellular Zn2+ influx in the hippocampus may be modified age-dependently, probably followed by modification of intracellular Zn2+ buffering that is closely linked with age-related cognitive decline and neurodegeneration. Reduction of intracellular Zn2+-buffering capacity may be linked with the pathophysiology of progressive neurodegeneration such as Alzheimer’s disease. This paper deals with age-dependent modification of intracellular Zn2+ buffering in the hippocampus and its impact. On the basis of the estimated impact, we propose a potential defense strategy against Zn2+-mediated neurodegeneration, i.e. , metallothionein induction in the hippocampus.
关键词：Zn2+;metallothionein;ZnAF-2DA;Zn2+ buffering;hippocampus;aging