Characteristic of Extracellular Zn Influx in the Middle-Aged Dentate Gyrus and Its Involvement in Attenuation of LTP.

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.