Deleterious effects of chronic mercury exposure on in vitro LTP, memory process, and oxidative stress

Abstract

Heavy metal contamination in aquatic environments plays an important role in the exposure of humans to these toxicants. Among these pollutants, mercury (Hg) is one main concern due to its high neurotoxicity and environmental persistence. Even in low concentrations, Hg bioaccumulation is a major threat to human health, with higher impact on populations whose diet has fish as chief consumption. Mercury compounds have high affinity for neuronal receptors and proteins, which gives Hg its cumulative feature and have the ability to cross cell membranes and blood–brain barrier to show their neurotoxicity. Intoxication with Hg increases levels of reactive oxygen species (ROS), thus depleting faster the resource of antioxidant proteins. To evaluate Hg-induced hippocampal ROS production, synaptic plasticity, anxiety, and memory, a total of 11 male Wistar rats were exposed to HgCl2 (Hg30 group) to produce a residual concentration of 8 ng/mL at the end of 30 days. Behavioral tests (plus-maze discriminative avoidance task), in vitro electrophysiology, and ROS assays were performed. Western blot assay showed decreased levels of antioxidant proteins GPx and SOD in Hg30 group. Increased ROS production was observed in the CA1 and CA3 regions in the Hg-exposed group. Plus-maze task detected long-term memory impairment in Hg30 group, linked to poorer in vitro long-term potentiation as compared to control group. Hg intoxication also promoted higher anxiety-like behavior in the exposed animals. In conclusion, our data suggests that low doses of HgCl2 resulted in impaired long-term memory and unbalance between decreased antioxidant protein expression and increased ROS production in the hippocampus.

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Author contributions statement

Authors’ contributions were as follows: D.V.V, F.A.S, A.C.F, and C.A.S designed the research; L.F.O and S.Z.R.G performed the electrophysiology experiments; L.F.O, L.D.R, and M.G.M conducted the behavior experiments; M.B.N, M.G.M, and K. Z performed biochemical experiments; L.F.O, L.D.R, M.G.M, M.B.N, and A.C.F analyzed the data; L.F.O, G.M.C, L.D.R, C.A.S, and F.A.S wrote the paper.

Funding

This work was supported by grants from Instituto Nacional de Neurociência Translacional (MCTIC/CNPq, Brazil) and CNPq (Brazil) to F.A.S. This study was financed in part by the Coordenaçāo de Aperfeiçoamento de Pessoal de Nível Superior–Brasil (CAPES–Finance Code 001) and by the State of Sao Paulo Research Support Foundation (FAPESP)

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Oliveira, L.F., Rodrigues, L.D., Cardillo, G.M. et al. Deleterious effects of chronic mercury exposure on in vitro LTP, memory process, and oxidative stress. Environ Sci Pollut Res 27, 7559–7569 (2020). https://doi.org/10.1007/s11356-019-06625-6

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Keywords

  • Mercury
  • Memory
  • Long-term potentiation
  • ROS
  • SOD
  • GPx