Department of Neurophysiology, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka, 422-8526, Japan.
Mol Neurobiol. 2018 Mar;55(3):2185-2195. doi: 10.1007/s12035-017-0472-z. Epub 2017 Mar 13.
An increased influx of extracellular Zn into neurons is a cause of cognitive decline. The influx of extracellular Zn into dentate granule cells was compared between young and middle-aged rats because of vulnerability of the dentate gyrus to aging. The influx of extracellular Zn into dentate granule cells was increased in middle-aged rats after injection of AMPA and high K into the dentate gyrus, but not in young rats. Simultaneously, high K-induced attenuation of LTP was observed in middle-aged rats, but not in young rats. The attenuation was rescued by co-injection of CaEDTA, an extracellular Zn chelator. Intracellular Zn in dentate granule cells was also increased in middle-aged slices with high K, in which the increase in extracellular Zn was the same as young slices with high K, suggesting that ability of extracellular Zn influx into dentate granule cells is greater in middle-aged rats. Furthermore, extracellular zinc concentration in the hippocampus was increased age-dependently. The present study suggests that the influx of extracellular Zn into dentate granule cells is more readily increased in middle-aged rats and that its increase is a cause of age-related attenuation of LTP in the dentate gyrus.
细胞外锌流入神经元是认知能力下降的一个原因。由于齿状回易受衰老影响，因此比较了年轻和中年大鼠齿状回颗粒细胞中外源锌的流入情况。向齿状回注射 AMPA 和高 K 后，中年大鼠细胞外锌流入增加，但年轻大鼠没有。同时，在中年大鼠中观察到高 K 诱导的 LTP 衰减，但在年轻大鼠中没有。用细胞外锌螯合剂 CaEDTA 共注射可挽救衰减。高 K 处理的中年切片中齿状回颗粒细胞内的锌也增加，其中细胞外锌的增加与高 K 处理的年轻切片相同，这表明中年大鼠细胞外锌流入齿状回颗粒细胞的能力更强。此外，海马细胞外锌浓度随年龄增长而增加。本研究表明，中年大鼠更容易增加细胞外锌流入齿状回颗粒细胞，其增加是齿状回 LTP 与年龄相关衰减的原因。
