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Sodium Butyrate Ameliorates Fluorosis-Induced Neurotoxicity by Regulating Hippocampal Glycolysis In Vivo

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Abstract

Fluorosis can induce neurotoxicity. Sodium butyrate (SB), a histone deacetylase inhibitor, has important research potential in correcting glucose metabolism disorders and is widely used in a variety of neurological diseases and metabolic diseases, but it is not yet known whether it plays a role in combating fluoride-induced neurotoxicity. This study aims to evaluate the effect of SB on fluoride neurotoxicity and the possible associated mechanisms. The results of HE staining and Morris water maze showed that, in mice exposed to 100 mg/L fluoride for 3 months, the hippocampal cells arranged in loosely with large cell gaps and diminished in number. One thousand milligram per kilogram per day SB treatment improved fluoride-induced neuronal cell damage and spatial learning memory impairment. Western blot results showed that the abundance of malate dehydrogenase 2 (MDH2) and pyruvate dehydrogenase (PDH) in the hippocampus of fluorosis mice was increased, the abundance of pyruvate kinase M (PKM), lactate dehydrogenase (LDH), hexokinase (HK), phosphatidylinositol 3-kinase (PI3K), phosphorylated Akt (P-AKT), and hypoxia-inducible factor 1α (HIF-1α) was inhibited, and the content of lactate and ATP was decreased. SB treatment reversed the decreased glycolysis in the hippocampus of fluorosis mice. These results suggested that SB could ameliorate fluorosis-induced neurotoxicity, which might be linked with its function in regulating glycolysis as well as inhibition of the PI3K/AKT/HIF-1α pathway.

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Sodium butyrate ameliorates fluorosis-induced neurotoxicity by regulating hippocampal glycolysis in vivo (created with MedPeer (www.medpeer.cn))

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Data Availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

This work was supported by grants from the National Natural Science Foundation of China (NSFC) (no. 81803200andno. 81803180), Liaoning Province Key Research and Development Program Guidance Plan (no. 2019JH8/10300047), Shenyang Science and Technology Plan Project (no. 21-108-9-11), Shenyang Middleyounger Scientific and Technological Innovation Support Plan (no. RC200238), Project of Education Department of Liaoning Province (no. SYYX202008), Youth Foundation of Liaoning Education Department (no. LJKQZ2021173), Science and Technology Innovation Fund for Postgraduates of Shenyang Medical College (no. Y20210503), and Natural Science Foundation of Liaoning Province (2022-NLTS-14-06).

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Y. L.: writing—original draft preparation; N. Y. and Z. W.: conceptualization, methodology, and funding acquisition; X. D. and J. L.: writing—review and editing and supervision; Y. D. and Y. W.: provided experimental method guidance; Y. Y and X. J.: data curation; Q. L.: generated and validated the mouse model.

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Correspondence to Xiaoxu Duan or Nan Yan.

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Li, Y., Wang, Z., Li, J. et al. Sodium Butyrate Ameliorates Fluorosis-Induced Neurotoxicity by Regulating Hippocampal Glycolysis In Vivo. Biol Trace Elem Res 201, 5230–5241 (2023). https://doi.org/10.1007/s12011-023-03583-6

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