miR-23b-5p: A potential biomarker in fluoride-induced neurological injury

Fluoride-induced neurological injury has garnered widespread attention, however, its underlying mechanisms remain unclear and there is still a lack of effective biomarkers for early identification. To investigate the molecular mechanism of fluoride neurotoxicity and identify potential intervention targets, we established a fluoride-exposed rat model and an SH-SY5Y cell model. We found that 25, 50, and 100 mg/L NaF resulted in impaired spatial memory capacity, disturbed neuronal alignment in the cerebral cortex and hippocampus, and reduced BDNF levels in rats' cerebral cortex. In vitro experiments demonstrated that fluoride increased apoptosis in SH-SY5Y cells. RNA sequencing revealed a significant elevation in miR-23b-5p levels in the brain tissues of fluoride-exposed rats. Subsequent validation experiments showed that fluoride upregulated miR-23b-5p expression in both rat brain tissues and SH-SY5Y cells. Notably, inhibition of miR-23b-5p led to increased brain-derived neurotrophic factor(BDNF) protein levels and reduced apoptosis in SH-SY5Y cells, indicating that miR-23b-5p served as a key regulator of fluoride-induced neurological injury. To further explore the potential of miR-23b-5p as a biomarker of fluoride-induced neurological injury, we conducted an epidemiologic survey in Wenshui County, Lvliang City, Shanxi Province, China. The results revealed that the expression level of miR-23b-5p in blood increased with the elevation of urinary fluoride, while serum BDNF expression decreased with increasing urinary fluoride, and miR-23b-5p exhibited a partial mediating effect between urinary fluoride and BDNF. This study identified a novel biomarker and potential intervention targets for fluoride-induced neurological injury.