title: Effects of copper on viability and functional properties of hippocampal neurons in vitro.
abstract: Copper (Cu2+) is an essential metal presented in the mammalian brain and released from synaptic vesicles following neuronal depolarization. However, the disturbance of Cu2+homeostasis results in neurotoxicity. In our study we performed for the first time a combined functional investigation of cultured hippocampal neurons under Cu2+exposure, its effect on spontaneous spike activity of hippocampal neuronal network cultured on multielectrode array (MEA), and development of long-term potentiation (LTP) in acute hippocampal slices in the presence of Cu2+. Application of 0.2mM CuCl2for 24h reduced viability of cultured neurons to 40±6%, whereas 0.01mM CuCl2did not influence significantly on the neuronal survival. However, exposure to the action of 0.01mM Cu2+resulted in pronounced reduction of network spike activity and abolished LTP induced by high-frequency stimulation of Schaffer's collaterals in CA1 pyramidal neurons of hippocampal slices. Antioxidant Trolox, the hydrosoluble vitamin E analogue, prevented neurotoxic effect and alterations of network activity under Cu2+exposure, but didn't change the impairment of LTP in Cu2+-exposured hippocampal slices. We hypothesized that spontaneous network neuronal activity probably is one of the potential targets of Cu2+-induced neurotoxicity, in which free radicals can be involved. At the same time, it may be suggested that Cu2+-induced alterations of long-lasting trace processes (like LTP) are not mediated by oxidative damage.
authors.affiliation: Research Center of Neurology, Moscow, Russia.
authors.forename: Marina R
authors.initials: MR
authors.lastname: Kapkaeva
authors.affiliation: Research Center of Neurology, Moscow, Russia.
authors.forename: Olga V
authors.initials: OV
authors.lastname: Popova
authors.affiliation: Research Center of Neurology, Moscow, Russia.
authors.forename: Rodion V
authors.initials: RV
authors.lastname: Kondratenko
authors.affiliation: Research Center of Neurology, Moscow, Russia.
authors.forename: Pavel D
authors.initials: PD
authors.lastname: Rogozin
authors.affiliation: Research Center of Neurology, Moscow, Russia.
authors.forename: Elisaveta E
authors.initials: EE
authors.lastname: Genrikhs
authors.affiliation: Research Center of Neurology, Moscow, Russia.
authors.forename: Elena V
authors.initials: EV
authors.lastname: Stelmashook
authors.affiliation: Research Center of Neurology, Moscow, Russia.
authors.forename: Vladimir G
authors.initials: VG
authors.lastname: Skrebitsky
authors.affiliation: Research Center of Neurology, Moscow, Russia.
authors.forename: Leonid G
authors.initials: LG
authors.lastname: Khaspekov
authors.affiliation: Research Center of Neurology, Moscow, Russia; Moscow State University, A.N. Belozersky Institute of Physico-Chemical Biology, Biological Faculty, Moscow, Russia. Electronic address: isaev@genebee.msu.ru.
authors.forename: Nickolay K
authors.initials: NK
authors.lastname: Isaev
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D003300:Copper / Q000633:toxicity*; D006624:Hippocampus / Q000187:drug effects; D017774:Long-Term Potentiation / Q000187:drug effects; D051379:Mice; D009474:Neurons / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects
chemical_list: D003300:Copper
keywords: Copper toxicity; Hippocampal neurons; LTP; Spike