Amyloid β1–42-Induced Rapid Zn2 Influx into Dentate Granule Cells Attenuates Maintained LTP Followed by Retrograde Amnesia

Abstract

On the basis of the evidence that amyloid β1–42 (Aβ1–42)-induced Zn2+ influx affects memory acquisition via attenuated long-term potentiation (LTP) induction, here we tested whether Aβ1–42-induced Zn2+ influx affects maintained LTP in freely moving rats, resulting in retrograde amnesia. Both maintained LTP and space memory were impaired by local injection of 250 μM ZnCl2 (2 μl) into the dentate gyrus, while maintained LTP was impaired by injection of either Aβ1–40 or Aβ1–42 (25 μM, 2 μl) into the dentate gyrus. Aβ1–40-induced impairment of maintained LTP was rescued by co-injection of CaEDTA, an extracellular Zn2+ chelator, but not by co-injection of ZnAF-2DA, an intracellular Zn2+ chelator,..