Low, but Not High, Doses of Copper Sulfate Impair Synaptic Plasticity in the Hippocampal CA1 Region In Vivo
- 97 Downloads
Previous studies have shown the inhibitory effect of the in vitro application of copper sulfate on hippocampal long-term potentiation. While in vivo administration of copper did not affect spatial learning and memory. To find possible answers to this controversial issue, we evaluate the effect of different doses of copper sulfate on in vivo long-term potentiation, synaptic transmission, and paired-pulse behavior of CA1 pyramidal cells. Thirty-two male Wistar rats were divided into four groups: control, 5, 10, and 15 mg of copper sulfate. Field excitatory postsynaptic potential from the stratum radiatum of CA1 neurons was recorded following Schaffer collateral stimulation in rats. Spike amplitude, long-term potentiation and paired-pulse index were measured in all groups. The results of this study showed that 5 mg/kg copper sulfate increased synaptic transmission and inhibited long-term potentiation and decreased the hippocampal paired-pulse ratio, while 10 and 15 mg/kg copper sulfate did not affect CA1 synaptic transmission properties. Low, but not high, doses of copper sulfate affect synaptic plasticity. This finding may explain the difference between the effect of copper on synaptic plasticity and spatial learning and memory.
KeywordsCopper sulfate Long-term potentiation Synaptic transmission Hippocampus
Financial support for this study was provided by Deputy Vice-chancellor of research on Arak University of Medical Sciences Grant # 628.
Compliance with Ethical Standards
Ethical approval for the study was provided by the Arak University of Medical Sciences Research Ethics Committee # 89-80-3.
Conflict of Interest
The authors declare that they have no conflict of interest.
- 1.Fujiwara N, Iso H, Kitanaka N, Kitanaka J, Eguchi H, Ookawara T, Ozawa K, Shimoda S, Yoshihara D, Takemura M, Suzuki K (2006) Effects of copper metabolism on neurological functions in Wistar and Wilson’s disease model rats. Biochem Biophys Res Commun 349(3):1079–1086. https://doi.org/10.1016/j.bbrc.2006.08.139 CrossRefPubMedGoogle Scholar
- 5.Vaz FNC, Fermino BL, Haskel MVL, Wouk J, de Freitas GBL, Fabbri R, Montagna E, Rocha JBT, Bonini JS (2017) The relationship between copper, iron, and selenium levels and Alzheimer disease. Biol Trace Elem Res:1–7. https://doi.org/10.1007/s12011-017-1042-y
- 13.Doreulee N, Yanovsky Y, Haas HL (1997) Suppression of long-term potentiation in hippocampal slices by copper. Hippocampus 7(6):666–669. https://doi.org/10.1002/(SICI)1098-1063(1997)7:6<666::AID-HIPO8>3.0.CO;2-C CrossRefPubMedGoogle Scholar
- 14.Kapkaeva MR, Popova OV, Kondratenko RV, Rogozin PD, Genrikhs EE, Stelmashook EV, Skrebitsky VG, Khaspekov LG, Isaev NK (2017) Effects of copper on viability and functional properties of hippocampal neurons in vitro. Exp Toxicol Pathol 69(5):259–264. https://doi.org/10.1016/j.etp.2017.01.011 CrossRefPubMedGoogle Scholar
- 17.Paxinos G, Watson C (2013) The rat brain in stereotaxic coordinates. Elsevier, Academic PressGoogle Scholar
- 21.Vlachová V, Zemková H, Vyklický L (1996) Copper modulation of NMDA responses in mouse and rat cultured hippocampal neurons. Eur J Neurosci 8(11):2257–2264. https://doi.org/10.1111/j.1460-9568.1996.tb01189.x CrossRefPubMedGoogle Scholar
- 25.Plech A, Klimkiewicz T, Jakrzewska H (2000) Neurotoxic effect of copper salts in rats. Pol J Environ Stud 9(4):301–304Google Scholar
- 29.Zeng X, Tietz EI (1997) Depression of early and late monosynaptic inhibitory postsynaptic potentials in hippocampal CA1 neurons following prolonged benzodiazepine administration: role of a reduction in Cl-driving force. Synapse 25(2):125–136. https://doi.org/10.1002/(SICI)1098-2396(199702)25:2<125::AID-SYN3>3.0.CO;2-E