Extracellular Zn2+-independently attenuated LTP by human amyloid β1-40 and rat amyloid β1-42

Abstract

Human amyloid-β_1-40 (Aβ_1-40) and rat Aβ_1-42 have lower affinity for extracellular Zn²⁺ than human Aβ_1-42. Here we report extracellular Zn²⁺-independent attenuation of dentate gyrus long-term potentiation (LTP) by human Aβ_1-40 and rat Aβ_1-42. On the basis of the data that dentate gyrus LTP is extracellular Zn²⁺-dependently attenuated after local injection of human Aβ_1-42 (25 pmol, 1 μl) into the dentate gyrus, which increases intracellular Zn²⁺ in the dentate gyrus, the toxicity of human Aβ_1-40 and rat Aβ_1-42 was compared in the in vivo system with human Aβ_1-42. Dentate gyrus LTP was attenuated after injection of human Aβ_1-40 and rat Aβ_1-42 (25 pmol, 1 μl) into the dentate gyrus, which did not increase intracellular Zn²⁺ in the dentate gyrus. The attenuated LTP was not rescued by co-injection of CaEDTA, an extracellular Zn²⁺ chelator. The present study suggests that human Aβ_1-40 and rat Aβ_1-42 affect cognitive activity via extracellular Zn²⁺-independent mechanism at low micromolar concentration.

Keywords: Dentate gyrus LTP; Human amyloid β(1-40); Rat amyloid β(1-42); Zn(2+).