Background
The intellectual loss induced by fluoride exposure has been extensively studied, but the association between fluoride exposure in different susceptibility windows and children’s intelligence is rarely reported. Hence, we conducted a cross-sectional study to explore the association between fluoride exposure in prenatal and childhood periods and intelligence quotient (IQ).
Methods
We recruited 633 local children aged 7–13 years old randomly from four primary schools in Kaifeng, China in 2017. The children were divided into four groups, of which included: control group (CG, n = 228), only prenatal excessive fluoride exposure group (PFG, n = 107), only childhood excessive fluoride exposure group (CFG, n = 157), both prenatal and childhood excessive fluoride exposure group (BFG, n = 141). The concentrations of urinary fluoride (UF) and urinary creatinine (UCr) were determined by fluoride ion-selective electrode assay and a creatinine assay kit (picric acid method), respectively. The concentration of UCr-adjusted urinary fluoride (CUF) was calculated. IQ score was assessed using the second revision of the Combined Raven’s Test-The Rural in China (CRT-RC2). Threshold and saturation effects analysis, multiple linear regression analysis and logistic regression analysis were conducted to analyze the association between fluoride exposure and IQ.
Results
The mean IQ score in PFG was respectively lower than those in CG, CFG and BFG (P < 0.05). The odds of developing excellent intelligence among children in PFG decreased by 51.1% compared with children in CG (OR = 0.489, 95% CI: 0.279, 0.858). For all the children, CUF concentration of ≥1.7 mg/L was negatively associated with IQ scores (β = − 4.965, 95% CI: − 9.198, − 0.732, P = 0.022). In children without prenatal fluoride exposure, every 1.0 mg/L increment in the CUF concentration of ≥2.1 mg/L was related to a reduction of 11.4 points in children’s IQ scores (95% CI: − 19.2, − 3.5, P = 0.005).
Conclusions
Prenatal and childhood excessive fluoride exposures may impair the intelligence development of school children. Furthermore, children with prenatal fluoride exposure had lower IQ scores than children who were not prenatally exposed; therefore the reduction of IQ scores at higher levels of fluoride exposure in childhood does not become that evident.
Using Sprague-Dawley rats and rat
PC12 cells treated with sodium
fluoride (NaF), we investigated the effects of SIK2-CRTC1 signaling
on the neurobehavioral toxicity induced by fluoride. The in
vivo results demonstrated that NaF treatment induced anxiety-
and depression-like behaviors in juvenile rats, resulting in histological
and ultrastructural abnormalities in the rat hippocampus and medial
prefrontal cortex. Moreover, NaF exposure induced neuronal loss and
excessive apoptosis. We also found that NaF elevated the expression
of SIK2 and reduced the expression of CRTC1, brain-derived neurotrophic
factor (BDNF), and VGF. The in vitro results showed
that NaF suppressed cell viability, induced SIK2-CRTC1 signaling dysfunction,
and caused excessive apoptosis in PC12 cells. Notably, targeted knockout
of SIK2 with SIK2-siRNA or blocking of SIK2-CRTC1 signaling with 7,8-dihydroxyflavone
(7,8-DHF) (as well as venlafaxine) can reduce apoptosis and increase
cell viability in vitro. These findings suggest that
neuronal death resulting from abnormal SIK2-CRTC1 signaling contributes
to neurobehavioral toxicity induced by fluoride.
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