Dissertation
Dissertation > Medicine, health > Internal Medicine > Endemiology

The Molecular Mechanism Intervention of Selenium on the Learning and Memory Injury by Drinking Water Fluorosis

Author WuYi
Tutor ZhangZiGui
School Zhejiang Normal University
Course Ecology
Keywords selenium fluorine hippocampus neurotoxicity [Ca2+] NF-κB
CLC R599
Type Master's thesis
Year 2011
Downloads 13
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Fluorine is the most electronegative metallic element widely distributed in nature, people exposure to fluoride through a variety of sources such as water, soil and air. The fluoride is a long-term accumulated poison, and excess intake of fluorine can cause skeletal fluorosis, dental fluorosis so far as to blood and nervous system damage. Nerve tissues are sensitive to fluorine particularly. Hippocampus as a target site of fluorosis in central nervous systems, which synaptic plasticity of nerve cells is vulnerable by affecting fluorine.Epidemiological field investigations and animal experiments have proved that a certain dose of selenium can alleviate fluorosis, make urinary fluoride excreting to correct the free radicals and lipid metabolism disorder, and significantly improve the brain damaged by fluoride. So far. antagonistic research about selenium on the phrenology system of fluoride poisoning body advanced considerably. Studies on the central nervous system have been reported but lacks of depth and system. In addition, in order to find the best anti-fluoride effect without producing toxic effects of selenium dose, it is necessary to get a smaller dose of selenium against fluoride, based on the 1.5 mg/L dose in the early studies.Methods:Sague-Dwley rats were administered with 50 mg/L of sodium fluoride solution, and with three concentrations (0.375 mg/L,0.75 mg/L,1.5 mg/L) of sodium selenite solution for 6-12 months. In this study, we also want to explore the synaptosomes [Ca2+] and the expression level of NF-κB p65 in hippocampus CA3 region to evaluate the effects of selenium on the damage of learning-memory ability of rats induced by fluoride, and to reveal the mechanism of selenium in ameliorating the damage of learning-memory ability induced by fluoride.Results:1. Opening test:Compared with the control group, the numbers of cells in 3 minutes running of the LSe-F and MSe-F rats in the novel environment increased significantly (P <0.05); the number of standing in selenium and HSe+F group increased significantly (P <0.05); buttresses and the numbers of rooming of the fluoride group increase significantly (P<0.05), while the MSe group was significantly lower than the fluoride group (P<0.05). These results suggest that although the behaviors of rats in the opening of individual indicators were significantly different, but considering the other indicators suggested that large individual differences in rats.2. Excessive fluoride intake can cause a damage of learning-memory ability of rats. Compared with the control group, on the third and fourth day of training, rats exposed to fluoride escape latency was significantly longer (p<0.05). the number of cross platform reduced significantly (p<0.05); The fourth day of training, LSe-F group escape latency decreased significantly and the number of cross platform increased significantly (p<0.05). the third day of training, compare with the control group, F-MSe group was significantly shorter (p<0.05), the number of crossing the platform increased significantly (p<0.05). indicating that low selenium has better prevention on the learning and memory damaged by fluorosis and medium selenium has better treatment.3. HE staining showed that chronic fluoride poisoning can damage the morphology of nerve cells in rats. Compared with the control group, rats exposed to fluoride sparse distribution of hippocampal cells. Change with time and dye fluorine dyed fluorine concentration of incremental and more significant. LSe. HSe+F and LSe-F group hippocampus CA3 area orderly and tightly packed cells, indicating that Appropriate concentrations of selenium can reduce fluorosis, protection of hippocampal cells.4. Ca2- concentration of synaptosomes results showed that fluoride treatment increased the Ca2+ overload. Compared with the control group. Ca2- concentration of fluoride group was significantly higher (P<0.05); low selenium can well control Ca2+ overload caused by fluorosis. Compared with the control group. LSe-F rat brain hippocampus [Ca2+] was significantly lower (p<0.05). Treatment group in each group Ca2+ concentration of synaptosomes were not significantly different, but the concentration of Ca2+ in the lowest selenium group, suggesting that selenium can inhibit fluoride induced Ca2+ concentration of synaptosomes increased.5. IHC results showed that compare with the control group, expression of NF-κB in hippocampus in fluoride group and high selenium group of rats was significantly higher (p<0.05), the expression of NF-κB of HSe+F significantly lower than the fluoride group (p<0.05). Expression of NF-κB in hippocampus of LSe-F was significantly lower than the control group (p<0.05). But the expression of NF-κB of F-LSe group was significantly higher than F-W group (p<0.05). High selenium would damage the brain and increased the expression of NF-κB, but HSe-F has shown antagonism. Low selenium can prevention of fluorosis, but LSe-F has no any curative effect.In conclusion, fluoride exposure on the central nervous system toxic effects can lead to neuronal cell morphology changes, causing hippocampal synaptosomes Ca2+ overload, and then lead to calcium signaling pathway in the expression of NF-κB p65 abnormal, leading to damage of learning-memory ability of rats. The amount of selenium can effectively alleviate such change, NF-κB p65 may be one of the molecular targets for Selenium treatment on brain injury caused by fluoride. Our results clearly indicated that the different concentration of selenium has different antagonistic fluorosis effect. However, the detailed mechanism of selenium antagonism against chronic fluorosis should be further explored.

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