| [Background] As an environmental toxicant, fluoride is harmful to bones and teeth. It has neurotoxicity, and one of the manifestation is the influence to learning and memory ability. People pay more and more attention to effects of fluoride on the IQ. Micrornas (miRNA) involved in regulating the growth and activity of the central nervous system, including the synaptic plasticity and neural cell differentiation, these activities are closely related to cognitive function. However whether the influence of fluoride on learning and memory is related to the miRNA is unclear. The study investigated whether the perinatal fluoride exposure caused changes in the spontaneous behavior, learning and memory ability, and anxiety behavior in offspring mice. In addition, if those were accompanied by the change in the miRNA and its target genes. Therefore, we attempted to discuss neurotoxic mechanism of fluorine from the transcription level, providing the basis for the prevention and treatment of fluorosis.[Method]After a week adaptability, the healthy ICR mice with sexual maturity were placed in one cage (male:female is 2:1). The day when vaginal were established was considered to be the pregnant day 0 (gestation day 0, GD0). Pregnant female mice were divided into four groups, including control group (distilled water) and three treated groups with sodium fluoride (NaF) of 25 mg/L,50mg/L and 100 mg/L in drinking water. They exposed to fluoride on pregnant day 7th by drinking water, and terminated on 21 st day after birth (PND unit 21). The spatial learning and memory of mice was tested by radial arm maze. HE staining and QPT-PCR were used to detect the morphology of hippocampus and the amount of relevant miRNA and mRNA expression in mice hippocampus.[Results] 1 The results of body weight:The maternal fluoride exposed decreased the body weight of offspring mice on PND3、PND6、PND9、PND12、PND15、PND18、PND21.2 The results of bone fluoride content:compared to the control group, the bone fluoride content was significantly increased in high fluoride group.3 The results of HE staining for hippocampus:the hippocampus structure of control group was clear and complete. The cell nucleus was round or oval and colored uniformly. The cell lined up tightly. The low fluoride group had no obvious change. In the middle and high fluoride groups, the number of nerve cells were reduced. The nucleus got small and irregular form, and the edges of the cell were fuzzy.4 The results of behavior test:There was a significant negative effect of maternal fluoride exposure on the open field behavior test in offspring mice on PND21, including the number of entrance in center. In the Radial-arm maze, exposure of high fluoride increased reference memory error, working memory errors, and total entrance center times. The result showed that fluoride impaired the learning and memory ability.5 QRT-PCR results of mice hippocampus miRNA expression showed that:the expression of miR-124 and miR-132 in hippocampus was significantly higher in high fluoride group.6 QRT-PCR results of mice hippocampus mRNA expression showed that:the express of DGCR8 was significantly increased. Mecp2 and TPH2 were significantly decreased. The CREB was significantly decreased. The results of glutamate receptor gene showed that AMPA1, AMPA2, and mGluR2 were decreased, the other three gene mGluR5, NMDAR2A, and NMDAR2B remained no change.[Conclusion] Perinatal exposure to fluoride can damage the mice’s ability of learning and memory. Its molecular mechanisms may involve in the changes in the expressions of miR-124, miR-132, glutamate receptors, and CREB. |
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