The accumulation of amyloid-β1-42 (Aβ1-42), a constituively-generated peptide, in the brain is considered an upstream event in pathogenesis of Alzheimer's disease. Aβ1-42-induced pathophysiology has been extensively studied in experimental mice and rats. However, neurotoxicity of murine Aβ1-42 is much less understood than human Aβ1-42. Here we report difference in ability for extracellular Zn2+ influx into dentate granule cells of rats between human and rat Aβ1-42 and its significance. Human Aβ1-42 rapidly increased intracellular Zn2+, which was determined with intracellular ZnAF-2, in dentate granule cells, 5 min after injection of Aβ1-42 (25 μM, 1 μl) into the dentate gyrus, while rat Aβ1-42 did not increase intracellular Zn2+. In vivo perforant pathway LTP was attenuated under pre-perfusion with 5 nM human Aβ1-42 in artificial cerebrospinal fluid (ACSF) containing 10 nM Zn2+, recapitulating the concentration of extracellular Zn2+, but not with 5 nM rat Aβ1-42 in ACSF containing 10 nM Zn2+. The present study suggests that rat Aβ1-42 has lower affinity for extracellular Zn2+ than human Aβ1-42 and does not capture Zn2+ in the extracellular compartment, resulting in no significant effect on cognitive activity of rat even in the range of very low nanomolar concentrations of endogenous Aβ1-42.

中文翻译：

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人和大鼠淀粉样蛋白β1-42胞外Zn2 +流入能力的差异及其意义。

组成性生成的肽淀粉样蛋白β1-42（Aβ1-42）在大脑中的积累被认为是阿尔茨海默氏病发病机理中的上游事件。已经在实验小鼠和大鼠中广泛研究了Aβ1-42诱导的病理生理学。然而，与人类Aβ1-42相比，对鼠Aβ1-42的神经毒性了解得多。在这里，我们报道了人与大鼠Aβ1-42之间的细胞外Zn2 +流入大鼠齿状颗粒细胞的能力差异及其意义。在将Aβ1-42（25μM，1μl）注入齿状回后5分钟，人Aβ1-42在齿状颗粒细胞中迅速增加了齿内颗粒细胞中的细胞内Zn2 +，而大鼠Aβ1-42却没有增加细胞内的Zn2 +。在含10 nM Zn2 +的人工脑脊液（ACSF）中用5 nM人Aβ1-42进行预灌注后，体内穿孔通路LTP减弱，重现了细胞外Zn2 +的浓度，但在含10 nM的ACSF中用5 nM大鼠Aβ1-42则没有。 nM Zn2 +。本研究表明，大鼠Aβ1-42对细胞外Zn2 +的亲和力低于人Aβ1-42，并且不捕获细胞外隔室中的Zn2 +，即使在非常低的纳摩尔浓度范围内，对大鼠的认知活性也没有显着影响。内源性Aβ1-42。