Molecular Neurobiology · Mar 13, 2017
Characteristic of Extracellular Zn²⁺ Influx in the Middle-Aged Dentate Gyrus and Its Involvement in Attenuation of LTP
By Takeda A, Koike Y, Osaw M et al.
An increased influx of extracellular Zn²⁺ into neurons is a cause of cognitive decline. The influx of extracellular Zn²⁺ 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 Zn²⁺ 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 Zn²⁺ chelator. Intracellular Zn²⁺ in dentate granule cells was also increased in middle-aged slices with high K⁺, in which the increase in extracellular Zn²⁺ was the same as young slices with high K⁺, suggesting that ability of extracellular Zn²⁺ 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 Zn²⁺ 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.