title: Transient increase in Zn2+ in hippocampal CA1 pyramidal neurons causes reversible memory deficit.
abstract: The translocation of synaptic Zn(2+) to the cytosolic compartment has been studied to understand Zn(2+) neurotoxicity in neurological diseases. However, it is unknown whether the moderate increase in Zn(2+) in the cytosolic compartment affects memory processing in the hippocampus. In the present study, the moderate increase in cytosolic Zn(2+) in the hippocampus was induced with clioquinol (CQ), a zinc ionophore. Zn(2+) delivery by Zn-CQ transiently attenuated CA1 long-term potentiation (LTP) in hippocampal slices prepared 2 h after i.p. injection of Zn-CQ into rats, when intracellular Zn(2+) levels was transiently increased in the CA1 pyramidal cell layer, followed by object recognition memory deficit. Object recognition memory was transiently impaired 30 min after injection of ZnCl(2) into the CA1, but not after injection into the dentate gyrus that did not significantly increase intracellular Zn(2+) in the granule cell layer of the dentate gyrus. Object recognition memory deficit may be linked to the preferential increase in Zn(2+) and/or the preferential vulnerability to Zn(2+) in CA1 pyramidal neurons. In the case of the cytosolic increase in endogenous Zn(2+) in the CA1 induced by 100 mM KCl, furthermore, object recognition memory was also transiently impaired, while ameliorated by co-injection of CaEDTA to block the increase in cytosolic Zn(2+). The present study indicates that the transient increase in cytosolic Zn(2+) in CA1 pyramidal neurons reversibly impairs object recognition memory.
authors.affiliation: Department of Medical Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, Global COE-21, Suruga-ku, Shizuoka, Japan. takedaa@u-shizuoka-ken.ac.jp
authors.forename: Atsushi
authors.initials: A
authors.lastname: Takeda
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Takada
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Nakamura
authors.forename: Miki
authors.initials: M
authors.lastname: Suzuki
authors.forename: Haruna
authors.initials: H
authors.lastname: Tamano
authors.forename: Masaki
authors.initials: M
authors.lastname: Ando
authors.forename: Naoto
authors.initials: N
authors.lastname: Oku
mesh_terms: D000818:Animals; D056547:CA1 Region, Hippocampal / Q000378:metabolism / Q000502:physiology*; D002712:Chlorides / Q000494:pharmacology; D003600:Cytosol / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism*; D017774:Long-Term Potentiation / Q000502:physiology; D008297:Male; D008568:Memory; D008569:Memory Disorders / Q000378:metabolism*; D017551:Microdialysis; D009474:Neurons / Q000378:metabolism*; D017966:Pyramidal Cells / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013569:Synapses / Q000502:physiology; D013997:Time Factors; D015032:Zinc / Q000737:chemistry / Q000378:metabolism*; D017967:Zinc Compounds / Q000494:pharmacology
chemical_list: D002712:Chlorides; D017967:Zinc Compounds; C016837:zinc chloride; D015032:Zinc