Effects Of High Fluoride On Children’s Intelligence And Programmed Death In Neurotoxicity In Rats

Part I Intellectual Influence of Exposed Water-borne High Fluoride in Tianjin on School-age ChildrenObjective To investigate whether there is a difference in urinary fluoride and IQ between children in relatively high drinking water fluorosis areas（water fluoride>2mg/L）and control areas（0.5<water fluoride<1 mg/L）in Baodi District,Tianjin,through epidemiological investigation.Methods The epidemiological survey was conducted in several areas with different water-borne fluorine concentrations in Baodi District,Tianjin.The data available to2260 children aged 7-12 years old were collected,including 1139 in the control group and 1121 in the drinking water-type high fluoride area.The IQ was measured by using modified raven progressive Matrix（CRT-C2,rural version）,and the fluoride ion selection electrode method was used for urine fluoride detection.Data were analyzed using an independent sample t test and multivariate linear regression model.Results Baseline data from the high fluoride group and the control group showed that only the age was different between the two groups（P<0.05）.The urinary fluoride concentration and the IQ score between in the high fluoride group and in the control group were different（P<0.05）;After adjusting for age,weight and hight,multiple linear model analysis showed that for every 1 mg/L increase in urine fluoride exposure in children,IQ decreased by 0.708 in children;with the increase of urinary fluoride concentration,children’s IQ showed a downward trend overall.Conclusion Long-term consumption of drinking water with high fluoride concentration in children may have a negative impact on children’s IQ.The dose-response relationship indicated that the IQ scores generally decreased with increasing urinary fluoride concentration.Part II Effects of Drinking High Fluoride Water during Pregnancy,Feeding and Adulthood on Neurotoxicity in Offspring Rats and Its Effect on Apoptosis and AutophagyObjective To investigate the effect of high fluoride water on spatial learning and memory ability,to explore the effect of high fluoride on thyroid function and the role of apoptosis and autophagy in hippocampus injury induced by high fluoride.Methods Healthy rats were selected and divided into four groups:control group（tap water,fluorine content 0.344 mg/L）and 10 mg/L,50 mg/L,100 mg/L three NaF dose groups,one week of free drinking water,male and female cage.After the mother is judged to be pregnant,she is raised separately.During the conception period,she continues to be dosed according to the set dose until the 21st day after the birth of the offspring.All the rats are separated by sex and dose,and the same treatment with the parent is continued.End of all fluorine exposure treatment on the 60th day after birth Weighing the body,the MWM was used to test the spatial learning and memory ability of the rats.After MWM,all the offspring rats were sacrificed.Blood was taken and serum TSH,FT₃ and FT₄ were determined by enzyme-linked immunosorbent assay;Thyroid tissue and hippocampus were taken and detection of apoptosis-related proteins in hippocampus by Western Blot expression levels of（Bcl-2 and Bax）and autophagy-related proteins（Beclin-1,mTOR,LC3-II and p62）.Results Compared with the control group,the urinary fluoride concentration of the offspring rats in the 100 mg/L and 50 mg/L NaF groups increased significantly（P<0.05）;Compared with the control group,the males The latency,path distance,time ratio and path ratio of the rats in the 100 mg/L NaF group reached significantly increased（P<0.05）;the overall trend of FT₃ increased（P>0.05）;Compared with the control group,the serum TSH and FT₄ concentration in the 100 mg/L group decreased significantly（P<0.05）;Compared with the control group,the expression levels of Bax,Beclin-1 and LC3-II in hippocampus of 100 mg/L and 50 mg/L NaF groups were significantly up-regulated（P<0.05）.Conversely,the expression levels of Bcl-2,mTOR and p62 protein in hippocampus of female and male offspring rats in 100mg/L and 50 mg/L NaF groups were significantly lower than those in the control group（P<0.05）.There was no significant difference in rat body weight,thyroid weight and brain weight（P>0.05）.Conclusion In the dose and mode of fluoride exposure in this study,high fluoride can lead to decreased secretion of TSH and FT₄ in the serum of progeny rats,and increased secretion of FT₃;High fluoride can cause spatial learning and memory impairment in offspring rats and the mechanism may be related to the enhancement of autophagy in hippocampus,and may be accompanied by apoptosis in hippocampus.