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Ghrelin attenuates methylmercury-induced oxidative stress in neuronal cells

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Abstract

Methylmercury (MeHg) is a global pollutant, which can cause damage to the central nervous system at both high-acute and chronic-low exposures, especially in vulnerable populations, such as children and pregnant women. Nowadays, acute-high poisoning is rare. However, chronic exposure to low MeHg concentrations via fish consumption remains a health concern. Current therapeutic strategies for MeHg poisoning are based on the use of chelators. However, these therapies have limited efficacy. Ghrelin is a gut hormone with an important role in regulating physiologic processes. It has been reported that ghrelin plays a protective role against the toxicity of several xenobiotics. Here, we explored the role of ghrelin as a putative protector against MeHg-induced oxidative stress. Our data show that ghrelin was able to ameliorate MeHg-induced reactive oxygen species (ROS) production in primary neuronal hypothalamic and hippocampal cultures. An analogous effect was observed in mouse hypothalamic neuronal GT 1–7 cells. Using this model, our novel findings show that antioxidant protection of ghrelin against MeHg is mediated by glutathione upregulation and induction of the NRF2/NQO1 pathway.

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Data Availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Acknowledgements

The author would like to thank Dr. Pamela Mellon from University of California, San Diego, for providing GT1-7 cells and the Analytical Imaging Facility of Albert Einstein College of Medicine (supported by a NCI Cancer Center Support Grant P30CA013330), specially to Andrea Briceno for her invaluable assistance with imaging.

Funding

This work was supported in part by a grant from the National Institute of Environmental Health Sciences (NIEHS) R01ES007331 (MA and ABB). This work was supported by the Ministry of Science and Higher Education of the Russian Federation within the framework of state support for the creation and development of World-Class Research Centers “Digital biodesign and personalized healthcare” 075–15-2020–926 (AVS).

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Authors and Affiliations

  1. Department of Molecular Pharmacology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY, 10461, USA

    Beatriz Ferrer, Harshini Suresh & Michael Aschner

  2. Laboratory of Molecular Dietetics, IM Sechenov First Moscow State Medical University, Moscow, Russia

    Alexey A. Tinkov & Michael Aschner

  3. Laboratory of Ecobiomonitoring and Quality Control, Yaroslavl State University, Yaroslavl, Russia

    Alexey A. Tinkov

  4. Laboratorio de Aminoácidos Excitadores/Laboratorio de Neurofarmacología Molecular Y Nanotecnología, Instituto Nacional de Neurología Y Neurocirugía, 14269, Mexico City, Mexico

    Abel Santamaria

  5. Departamento de Bioquímica E Biologia Molecular, Universidade Federal de Santa Maria, Santa Maria, Rio Grande do Sul, Brazil

    João Batista Rocha

  6. World-Class Research Center “Digital Biodesign and Personalized Healthcare”, IM Sechenov First Moscow State Medical University (Sechenov University), 119435, Moscow, Russia

    Anatoly V. Skalny

  7. Department of Bioelementology, KG Razumovsky Moscow State University of Technologies and Management, Moscow, Russia

    Anatoly V. Skalny

  8. School of Health Sciences, Purdue University, West Lafayette, IN, USA

    Aaron B. Bowman

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  1. Beatriz Ferrer
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  8. Michael Aschner
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Contributions

B.F. and M.A. conceived the project. H.S. and B.F. conducted the experiments and collected the data. B.F. analyzed the data and wrote the manuscript. A.S., A.V.S. and J.B.R. revised the manuscript. A.B.B., A.V.S. and M.A. edited the manuscript secured funding. All authors read and approved the final version of the manuscript.

Corresponding authors

Correspondence to Beatriz Ferrer or Michael Aschner.

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As already mentioned in the “Materials and Methods” section, part of this study design of rat primary neuronal cultures isolation from rat was reviewed and approved by the Institutional Animal Care and Use Committees (IACUC) of Albert Einstein College of Medicine.

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Ferrer, B., Suresh, H., Tinkov, A.A. et al. Ghrelin attenuates methylmercury-induced oxidative stress in neuronal cells. Mol Neurobiol 59, 2098–2115 (2022). https://doi.org/10.1007/s12035-022-02726-5

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