title: Amyloid β-mediated Zn2+ influx into dentate granule cells transiently induces a short-term cognitive deficit.
abstract: We examined an idea that short-term cognition is transiently affected by a state of confusion in Zn2+ transport system due to a local increase in amyloid-β (Aβ) concentration. A single injection of Aβ (25 pmol) into the dentate gyrus affected dentate gyrus long-term potentiation (LTP) 1 h after the injection, but not 4 h after the injection. Simultaneously, 1-h memory of object recognition was affected when the training was performed 1 h after the injection, but not 4 h after the injection. Aβ-mediated impairments of LTP and memory were rescued in the presence of zinc chelators, suggesting that Zn2+ is involved in Aβ action. When Aβ was injected into the dentate gyrus, intracellular Zn2+ levels were increased only in the injected area in the dentate gyrus, suggesting that Aβ induces the influx of Zn2+ into cells in the injected area. When Aβ was added to hippocampal slices, Aβ did not increase intracellular Zn2+ levels in the dentate granule cell layer in ACSF without Zn2+, but in ACSF containing Zn2+. The increase in intracellular Zn2+ levels was inhibited in the presence of CaEDTA, an extracellular zinc chelator, but not in the presence of CNQX, an AMPA receptor antagonist. The present study indicates that Aβ-mediated Zn2+ influx into dentate granule cells, which may occur without AMPA receptor activation, transiently induces a short-term cognitive deficit. Extracellular Zn2+ may play a key role for transiently Aβ-induced cognition deficits.
authors.affiliation: Department of Neurophysiology, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan; Department of Medical Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Takeda
authors.affiliation: Department of Medical Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Nakamura
authors.affiliation: Department of Medical Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Fujii
authors.affiliation: Department of Medical Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.
authors.forename: Chihiro
authors.initials: C
authors.lastname: Uematsu
authors.affiliation: Department of Neurophysiology, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Minamino
authors.affiliation: Oxidation Biology Unit, The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Adlard
authors.affiliation: Oxidation Biology Unit, The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Ashley I
authors.initials: AI
authors.lastname: Bush
authors.affiliation: Department of Neurophysiology, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan; Department of Medical Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.
authors.forename: Haruna
authors.initials: H
authors.lastname: Tamano
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D002413:Cations, Divalent / Q000378:metabolism; D002614:Chelating Agents / Q000627:therapeutic use; D018891:Dentate Gyrus / Q000378:metabolism* / Q000503:physiopathology; D017774:Long-Term Potentiation; D008297:Male; D008568:Memory / Q000187:drug effects; D008569:Memory Disorders / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000378:metabolism; D015032:Zinc / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D002413:Cations, Divalent; D002614:Chelating Agents; D018091:Receptors, AMPA; D015032:Zinc