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Exercise Alleviates Fluoride-Induced Learning and Memory Impairment in Mice: Role of miR-206-3p and PREG

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Abstract

Fluorosis decreases the learning and memory ability in humans and animals, while exercise can reduce the risk of cognitive decline. However, the effect of exercise on learning and memory in fluoride-exposed mice is unclear. For this purpose, in this study, mice were randomly allotted into four groups (16 mice per group, half male and half female): control group (group C), fluoride group (group F, 100 mg/L sodium fluoride (NaF)), exercise group (group E, treadmill exercise), and E plus F group (group EF, treadmill exercise, and 100 mg/L NaF). During 6 months of exposure, exercise alleviated the NaF-induced decline in memory and learning. In addition, NaF induced injuries in mitochondria and myelin sheath ultrastructure and reduced the neurons number, while exercise restored them. Metabolomics results showed that phosphatidylethanolamine, pregnenolone (PREG), and lysophosphatidic acid (LysoPA) were altered among groups C, F, and EF. Combined with previous studies, it can be suggested that PREG might be a biomarker in response to exercise-relieving fluorine neurotoxicity. The miRNA sequencing results indicated that in the differently expressed miRNAs (DEmiRNAs), miR-206-3p, miR-96-5p, and miR-144-3p were shared in groups C, F, and EF. After the QRT-PCR validation and in vitro experiments, it was proved that miR-206-3p could reduce cell death and regulate AP-1 transcription factor subunit (JunD) and histone deacetylase 4 (HDAC4) to alleviate fluoride neurotoxicity. To sum up, the current study reveals that exercise could alleviate NaF-induced neurotoxicity by targeting miR-206-3p or PREG, which will contribute to revealing the pathogenesis and therapeutic method of fluoride neurotoxicity.

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Data Availability

All data generated or analyzed during this study are included in the published article and its supplementary information fles. The raw data of the paper are available upon request from the corresponding author.

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Acknowledgements

This work were supported by the Research Project Supported by the Shanxi Scholarship Council of China (HGKY2019042), the Scientific Research Innovation Project in College of Veterinary Medicine of Shanxi Agricultural University (DY-M009).

Funding

This work was supported by the Research Project Supported by the Shanxi Scholarship Council of China (HGKY2019042) and the Scientific Research Innovation Project in College of Veterinary Medicine of Shanxi Agricultural University (DY-M009).

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Authors and Affiliations

  1. College of Veterinary Medicine, Shanxi Agricultural University, Taigu, Jinzhong, 030801, Shanxi, China

    Lei Chai, Qiqi Cao, Ke Liu, Run Zhu, Hao Li, Yanghuan Yu, Jixiang Wang, Ruiyan Niu, Ding Zhang, Bo Yang, Mohammad Mehdi Ommati & Zilong Sun

  2. Henan Key Laboratory of Environmental and Animal Product Safety, Henan University of Science and Technology, Luoyang, 471000, Henan, China

    Mohammad Mehdi Ommati

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  11. Mohammad Mehdi Ommati
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  12. Zilong Sun
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Contributions

LC: the design of the study, acquisition of data, analysis and interpretation of data, and drafting the manuscript; QC: technical support and interpretation of data; KL: technical support; RZ: technical support and acquisition of data; HL: acquisition of data; YY: interpretation of data; JW: analysis and interpretation of data; RN: analysis data and revising the manuscript; DZ: interpretation of data; BY: analysis and interpretation of data and revising the manuscript; MMO: validation, analysis and interpretation of data, and review and editing; ZS: the conception of the study, administration of the project, and drafting and revising the manuscript.

Corresponding authors

Correspondence to Mohammad Mehdi Ommati or Zilong Sun.

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Highlights

• Exercise alleviated NaF-induced learning and memory impairment in mice.

• Exercise restored NaF-caused variations in hippocampal ultrastructure.

• Exercise could alleviate NaF-induced neurotoxicity mainly through PREG or miR-206-3p.

• PREG might be a biomarker in response to exercise-relieving fluoride neurotoxicity.

• miR-206-3p could regulate JunD and HDAC4 to alleviate fluoride neurotoxicity.

Supplementary Information

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Supplementary file1 (RAR 495 KB)

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Chai, L., Cao, Q., Liu, K. et al. Exercise Alleviates Fluoride-Induced Learning and Memory Impairment in Mice: Role of miR-206-3p and PREG. Biol Trace Elem Res 202, 5126–5144 (2024). https://doi.org/10.1007/s12011-024-04068-w

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  • DOI: https://doi.org/10.1007/s12011-024-04068-w

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