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2-BFI Provides Neuroprotection Against Fluorosis by Stabilizing Endoplasmic Reticulum–Mitochondria Contact Sites and Inhibiting Activation of the NLRP3 Inflammasome

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Abstract

2-(2-benzofu-ranyl)-2-imidazoline (2-BFI) is a drug that has attracted much attention in recent years. It has a therapeutic effect on brain diseases in animal models such as Alzheimer’s disease and cerebral infarction. However, whether 2-BFI affords neuroprotection against the toxicity of fluoride, which can cross the blood–brain barrier and cause neurological dysfunction is not known. We investigated the cell viability and apoptosis of SH-SY5Y cells and primary cultures of cortical neurons exposed to fluoride, and 2-BFI was used to protect both two kinds of cells against the effects of fluoride. We found that 2-BFI can provide neuroprotection on SH-SY5Y cells and primary cultures of cortical neurons upon fluorosis by maintaining the stability of endoplasmic reticulum–mitochondria contact sites and inhibiting activation of the NLR family pyrin domain containing 3 (NLRP3) inflammasome. This study may provide a new method for protecting against the neurotoxicity induced by fluoride exposure.

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Data Availability

The data supporting the conclusions of this article will be made available from the corresponding author on reasonable request.

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Acknowledgements

We are thankful for the technical support provided by Professor Ruiqin Yao (Xuzhou Medical University).

Funding

This study was supported (HAB201932) by the Natural Science Foundation of Huai’an City, Jiangsu Province, China. and (XWKYHT20200064) Medical Science and Technology Innovation Project of Xu’zhou Health Commission for Young Scholars.

Author information

Author notes

  1. Rui Chen, Wan Xu and Yifu Sun have contributed equally to this work.

Authors and Affiliations

  1. Department of Neurology, The Second People’s Hospital of Huai’an and The Affiliated Huai’an Hospital of Xuzhou Medical University, Huai’an, Jiangsu, China

    Rui Chen, Yifu Sun & Zhongwen Zhi

  2. Department of Psychiatry and Psychology, Xuzhou Medical University Affiliated Xuzhou Oriental Hospital, Xuzhou, Jiangsu, China

    Caiyi Zhang

  3. Department of Neurology, Hongze Huai’an District People’s Hospital, Huai’an, Jiangsu, China

    **aohong Tang

  4. Department of Psychiatry and Mental Health, The Affiliated Xuzhou Municipal Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China

    Wan Xu

  5. Department of Gastroenterology, Lianshui County People’s Hospital Affiliated to Kangda College of Nan**g Medical University, Huai’an, Jiangsu, China

    Rongrong Zhi

  6. Department of Neurosurgery, The Second People’s Hospital of Huai’an and The Affiliated, Huai’an Hospital of Xuzhou Medical University, Huai’an, Jiangsu, China

    Peng **e

Authors
  1. Rui Chen
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  2. Wan Xu
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Contributions

RC: investigation, and writing of the original draft. WX and YS: investigation and writing (review and editing). RZ and ZZ: data analyses. PX: data analyses, resource acquisition, experimental validation, software accrual. CZ and XT: conceptualization and supervision of the study.

Corresponding authors

Correspondence to **aohong Tang or Caiyi Zhang.

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Chen, R., Xu, W., Sun, Y. et al. 2-BFI Provides Neuroprotection Against Fluorosis by Stabilizing Endoplasmic Reticulum–Mitochondria Contact Sites and Inhibiting Activation of the NLRP3 Inflammasome. Neurochem Res 48, 591–603 (2023). https://doi.org/10.1007/s11064-022-03781-z

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