Effects of copper on viability and functional properties of hippocampal neurons in vitro

• Published in: Experimental and toxicologic pathology : official journal of the Gesellschaft für Toxikologische Pathologie Vol. 69; no. 5; pp. 259 - 264
• Main Authors: Kapkaeva, Marina R., Popova, Olga V., Kondratenko, Rodion V., Rogozin, Pavel D., Genrikhs, Elisaveta E., Stelmashook, Elena V., Skrebitsky, Vladimir G., Khaspekov, Leonid G., Isaev, Nickolay K.
• Format: Journal Article
• Language: English
• Published: Germany Elsevier GmbH 14-06-2017
• Subjects: Animals; Cell Survival - drug effects; Copper - toxicity; Hippocampal neurons; Hippocampus - drug effects; Long-Term Potentiation - drug effects; LTP; Mice; Neurons - drug effects; Spike; Synaptic Transmission - drug effects; Spike; Copper toxicity; LTP; Hippocampal neurons
• ISSN: 0940-2993; 1618-1433
• DOI: 10.1016/j.etp.2017.01.011

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 CuCl2 for 24h reduced viability of cultured neurons to 40±6%, whereas 0.01mM CuCl2 did 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.