title: Biphasic Effects of Copper on Rat Learning and Memory in the Morris Water Maze.
abstract: Dysregulation of copper (Cu) metabolism interrupts neuron function, and subsequently results in neuron degeneration, necrosis, and gliocyte hyperplasia. To further explore the effects of hippocampal Cu concentration on learning and memory, Sprague-Dawley (SD) rats were given once-daily intraperitoneal injections of Copper(II) acetate (Cu(OAc)2) at doses of 0.2, 2, or 20mg/Kg over 5 days. Ultrasonic oscillation dialysis was used to determine the free Cu by graphite furnace atomic absorption spectrometry (GFAAS). Cu administration induced a dose-dependent increase in total hippocampal Cu. However, free hippocampal Cu was found to increase only at the lower concentration of Cu(OAc)2 (0.2 mg/Kg) but decrease at higher concentrations of Cu(OAc)2 (2 and 20 mg/Kg). Higher doses of Cu(OAc)2 (2-20mg/Kg) decreased superoxide dismutase-1 (SOD1) activity, increased both malondialdehyde (MDA) levels and the glutamate/γ-aminobutyric acid (Glu/GABA) ratio, and impaired spatial cognition. However, the lower dose of Cu(OAc)2 (0.2 mg/Kg) showed the opposite effects. This biphasic effect might be attributed to free hippocampal Cu levels and corresponding alterations of Glu/GABA ratio and SOD1 activity.
authors.affiliation: Bio-analytical Laboratory, Shantou University Medical College, Shantou, PR China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: First Affiliated Hospital, Shantou University Medical College, Shantou, PR China.
authors.forename: Wulin
authors.initials: W
authors.lastname: Lu
authors.affiliation: Second Affiliated Hospital, Shantou University Medical College, Shantou, PR China.
authors.forename: Ming
authors.initials: M
authors.lastname: Han
authors.affiliation: Bio-analytical Laboratory, Shantou University Medical College, Shantou, PR China.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.affiliation: Bio-analytical Laboratory, Shantou University Medical College, Shantou, PR China.
authors.forename: Hongjun
authors.initials: H
authors.lastname: Luo
authors.affiliation: Bio-analytical Laboratory, Shantou University Medical College, Shantou, PR China.
authors.forename: Weiqiu
authors.initials: W
authors.lastname: Li
authors.affiliation: Bio-analytical Laboratory, Shantou University Medical College, Shantou, PR China whluo@stu.edu.cn g_zxlin@stu.edu.cn.
authors.forename: Wenhong
authors.initials: W
authors.lastname: Luo
authors.affiliation: Bio-analytical Laboratory, Shantou University Medical College, Shantou, PR China whluo@stu.edu.cn g_zxlin@stu.edu.cn.
authors.forename: Zhexuan
authors.initials: Z
authors.lastname: Lin
mesh_terms: D000818:Animals; D003300:Copper / Q000008:administration & dosage / Q000494:pharmacology*; D003956:Dialysis; D006108:Graphite; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D018782:Maze Learning / Q000187:drug effects*; D008568:Memory / Q000187:drug effects*; D018377:Neurotransmitter Agents / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D013054:Spectrophotometry, Atomic; D013482:Superoxide Dismutase / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D018377:Neurotransmitter Agents; D008315:Malondialdehyde; D005680:gamma-Aminobutyric Acid; D006108:Graphite; D003300:Copper; D013482:Superoxide Dismutase
keywords: Biphasic effects; Copper; Hippocampus; Learning and memory