Sirt3-mediated mitochondrial dysfunction is involved in fluoride-induced cognitive deficits.
Level 5 - mechanism / opinion, no new human data
Preclinical animal and in vitro mechanistic study without human clinical data
PubMed 34780879 · doi:10.1016/j.fct.2021.112665
What was done
C57BL/6 mice were orally administered sodium fluoride (NaF) at doses of 25, 50, and 100 mg/L for 90 days to evaluate cognitive deficits and neural/synaptic injury. In parallel, cultured human neuroblastoma SH-SY5Y cells were exposed to 110 mg/L NaF for 24 hours with or without Sirt3 overexpression to assess mitochondrial function, antioxidant enzyme activity, mitochondrial DNA (mtDNA) transcription, and protein acetylation (SOD2 and FoxO3A).
What was found
The abstract reports directional changes without numeric values or effect sizes. Chronic fluoride exposure induced cognitive deficits and neural/synaptic injury in mice. In both mouse brains and SH-SY5Y cells, fluoride downregulated Sirt3 expression, increased SOD2 and FoxO3A acetylation, lowered mitochondrial antioxidant enzyme activity and mtDNA transcription, and induced mitochondrial dysfunction. Overexpression of Sirt3 in SH-SY5Y cells significantly attenuated fluoride-induced impairments in radical scavenging, mtDNA transcription, and mitochondrial function.
Why it matters
This study highlights Sirt3 inhibition and resulting mitochondrial oxidative stress as a potential molecular pathway underlying fluoride-induced neurotoxicity and cognitive impairment in preclinical models.
Limits
The study is entirely preclinical, using mouse models and an immortalized neuroblastoma cell line, meaning relevance to human exposure levels remains uncertain. The abstract omits sample sizes, exact dose-response metrics, and quantitative statistical values.
Cited by
- supports Fluoride damages the myelin sheath of neurons and impairs mitochondrial integrity in the brain.