Sodium butyrate ameliorates fluorosis-induced neurotoxicity by regulating hippocampal glycolysis in vivo

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 three months, the hippocampal cells arranged in loosely with large cell gaps and diminished in number. In addition, 1000 mg/kg/day SB treatment improved fluoride-induced neuronal cell damage and spatial learning memory impairment. Western blotting showed that the abundance of malate dehydrogenase 2 (MDH2) and pyruvate dehydrogenase (PDH) in the hippocampus of mice increased after fluorosis, while the abundance of pyruvate kinase M (PKM), lactate dehydrogenase (LDH) and hexokinase (HK) decreased. SB treatment reversed the decreased glycolysis in the hippocampus of fluorosis mice. We suspected that the PI3K/AKT/HIF-1α pathway may be involved in mediating the protective effects of SB against fluorosis invasion in the hippocampus. 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.