Biological Trace Element Research

, Volume 155, Issue 2, pp 253–260 | Cite as

Effect of Selenium on Fluoride-Induced Changes in Synaptic Plasticity in Rat Hippocampus

  • Wei Qian
  • Keke Miao
  • Tao Li
  • Zigui ZhangEmail author


This study was conducted to further explore the effect of selenium on fluoride-induced changes in the synaptic plasticity in rat hippocampus. Animals were randomly divided into control group, F group (sodium fluoride: 50 mg/L), three Se groups (sodium selenite: 0.375, 0.75, and 1.5 mg/L), and three F + Se groups (sodium fluoride: 50 mg/L; sodium selenite: 0.375, 0.75, and 1.5 mg/L) and subjected to an exposure time of 6 months. The changes in synaptic plasticity in rat hippocampus were observed by electron microscopy. Compared with the fluoride group, the length of the synaptic active zone and the thickness of the postsynaptic density (PSD) increased significantly, whereas the width of the synaptic cleft decreased with high significance in the F + Se (0.75 mg/L) group. Moreover, the nitric oxide synthase activity and the nitric oxide content in the hippocampus decreased significantly in the F + Se (0.75 and 1.5 mg/L) groups. Furthermore, reverse transcriptase polymerase chain reaction and Western blot analyses showed that postsynaptic density-93 (PSD-93) expression in the hippocampus was increased significantly, whereas postsynaptic density-95 (PSD-95) expression decreased significantly in the fluoride group compared with the control group. The PSD-93 expression was inhibited in the three F + Se groups, whereas the opposite result was observed in PSD-95 expression. Based on the results, the optimal selenium dosage range that can antagonize the neurotoxicity of fluorosis is from 0.75 to 1.5 mg/L. The changes in PSD-93 expression may be the key factor to fluoride-induced central nervous toxicity and the effect of selenium intervention.


Fluoride Selenium Hippocampus Brain damage Antagonistic 



This research was supported by the National Natural Science Foundation of China (no. 81273015).

Conflict of Interest



  1. 1.
    Sharma JD, Sohu D, Jain P (2009) Prevalence of neurological manifestation in a human population exposed to fluoride in drinking water. Fluoride 42(2):127–132Google Scholar
  2. 2.
    Shivarajashankara YM, Shivashankara AR, Bhat PG et al (2002) Brain lipid peroxidation and antioxidant systems of young rats in chronic fluoride intoxication. Fluoride 35(3):197–203Google Scholar
  3. 3.
    Shashi A (2003) Histopathological investigation of fluoride induced neurotoxicity in rabbits. Fluoride 36(2):95–105Google Scholar
  4. 4.
    Bhatnagar M, Rao P, Sushma J et al (2002) Neurotoxicity of fluoride: neurodegeneration in hippocampus of female mice. Indian J Exp Biol 40(5):546–554PubMedGoogle Scholar
  5. 5.
    Bhatnagar M, Rao P, Saxena A et al (2006) Biochemical changes in brain and other tissues of young adult female mice from fluoride in their drinking water. Fluoride 39(4):280–284Google Scholar
  6. 6.
    Wu CX, Gu XL, Ge YM et al (2006) Effects of high fluoride and arsenic on brain biochemical indexes and learning-memory in rats. Fluoride 39(4):274–279Google Scholar
  7. 7.
    Chirumari K, Reddy PK (2007) Dose-dependent effects of fluoride on neurochemical milieu in the hippocampus and neocortex of rat brain. Fluoride 40(2):101–110Google Scholar
  8. 8.
    Xiang Q, Liang Y, Chen L et al (2003) Effect of fluoride in drinking water on children's intelligence. Fluoride 36(2):84–94Google Scholar
  9. 9.
    Lu Y, Sun ZR, Wu LN et al (2000) Effect of high-fluoride water on intelligence in children. Fluoride 33(2):74–78Google Scholar
  10. 10.
    Sho K, Masahiko S, Nozomu M (2012) Protein oxidation inhibits NO-mediated signaling pathway for synaptic plasticity. Neurobiol Aging 33(3):535–545CrossRefGoogle Scholar
  11. 11.
    Hawkins RD (2008) Transsynaptic signaling by NO during learning-related synaptic plasticity. Learn Mem Compr Ref 4:793–802CrossRefGoogle Scholar
  12. 12.
    Kihoon H, Eunjoon K (2008) Synaptic adhesion molecules and PSD-95. Prog Neurobiol 84:263–283CrossRefGoogle Scholar
  13. 13.
    Samah SO, Zeynab KE (2012) Protective effect of vitamin E and selenium combination on deltamethrin-induced reproductive toxicity in male rats. Exp Toxicol Pathol 64(7–8):813–819Google Scholar
  14. 14.
    Lewin MH, Arthur JR, Riemersma RA et al (2002) Selenium supplementation acting through the induction of thioredoxin reductase and glutathione peroxidase protects the human endothelial cell line EAhy926 from damage by lipid hydroperoxides. Biochim Biophys Acta 1593(1):85–92PubMedCrossRefGoogle Scholar
  15. 15.
    Feng P, Wei JR, Zhang ZG (2011) Intervention of selenium on chronic fluorosis-induced injury of blood antioxidant capacity in rats. Biol Trace Elem Res 144(1–3):1024–1031PubMedCrossRefGoogle Scholar
  16. 16.
    Feng P, Wei JR, Zhang ZG (2012) Influence of selenium and fluoride on blood antioxidant capacity of rats. Exp Toxicol Pathol 64(6):565–568PubMedCrossRefGoogle Scholar
  17. 17.
    Essatara MB, Morley JE, Levine AS et al (1984) The role of the endogenous opiates in zinc deficiency anorexia. Physiol Behav 32(3):475–478PubMedCrossRefGoogle Scholar
  18. 18.
    Chen YC, Han TZ, Shen JX et al (1999) A quantitative study on the synaptic ultrastructural alterations in visual cortex in the maintenance of ltp. Acta Physiol Sin 51(1):73–79Google Scholar
  19. 19.
    Kobayashi CA, Leite AL, Silva TL et al (2009) Proteomic analysis of kidney in rats chronically exposed to fluoride. Chem-Biol Inter 180(2):305–311CrossRefGoogle Scholar
  20. 20.
    Xiong XZ, Liu JL, He WH et al (2007) Dose-effect relationship between drinking water fluoride levels and damage to liver and kidney functions in children. Environ Res 103(1):112–116PubMedCrossRefGoogle Scholar
  21. 21.
    Zhu WJ, Zhang J, Zhang ZG (2011) Effects of fluoride on synaptic membrane fluidity and PSD-95 expression level in rat hippocampus. Biol Tr Elem Res 139(2):197–203CrossRefGoogle Scholar
  22. 22.
    Luo HJ, Ji YH (2000) Biological role and significance of selenium. Stud Trace Elem Health 17(2):70–72Google Scholar
  23. 23.
    Han B, Yoon SS, Wu PF et al (2006) Role of selenium in alteration of erythrocyte parameters in bovine fluorosis. Asian Australas J Anim Sci 19(6):865–872Google Scholar
  24. 24.
    Abdella A, Gan L, Liu Q et al (2003) The antioxidation of breviscapine and its antagonist of selenium on liver toxicity in rat. Chin Pharmacol Bull 19(1):113–115Google Scholar
  25. 25.
    Wang GZ, Niu ZX (2011) The progress study of toxicity of selenium. Northwest Pharm J 25(3):237–238Google Scholar
  26. 26.
    Zhu WJ, Zhang ZG, Shen XY (2009) Pathogenesis of fluorosis and the role of selenium against fluoride. Chin J Endemiol 28(6):704–706Google Scholar
  27. 27.
    Holger S, Lirija A, Esra B et al (2006) Involvement of selenoprotein P in protection of human astrocytes from oxidative damage. Free Radic Biol Med 40(9):1513CrossRefGoogle Scholar
  28. 28.
    Zhang ZG, Shen XY, Xu XL (2001) Effects of selenium on the damage of learning-memory ability of mice induced by fluoride. J Hyg Res 30(3):144–146Google Scholar
  29. 29.
    Frick KM, Fernandez SM (2003) Enrichment enhances spatial memory and increases synaptophysin levels in aged female mice. Neurobiol Aging 24(4):615–626PubMedCrossRefGoogle Scholar
  30. 30.
    Xu XH (2003) Investigation on effects of puerarin against memory impairment in mice induced by chronic alcoholism. Chin J Pharm 38(1):31–34Google Scholar
  31. 31.
    Zhang ZG, Xu XL, Shen XY et al (1999) Effect of fluoride exposure on synaptic structure of brain areas related to learning–memory in mice. J Hyg Res 28(4):210–212Google Scholar
  32. 32.
    Wyneken U, Smalla KH, Marengo JJ et al (2001) Kainate-induced seizures alter protein composition and N-methyl-D-aspartic acid receptor function of rat forebrain postsynaptic densities. Neuroscience 102(1):65–74PubMedCrossRefGoogle Scholar
  33. 33.
    Myried N, Zhang WN, Joram F et al (2007) Differential expression of PSD proteins in age-related spatial learning impairments. Neurobiol Aging 28(1):143–155CrossRefGoogle Scholar
  34. 34.
    Shashi A, Singh JP, Thapar SP (1994) Effect of long-term administration of fluoride on levels of protein, free amino acids, and RNA in rabbit brain. Fluoride 27(3):155–159Google Scholar
  35. 35.
    Çiğdem GS, Serdar K, Orhan A et al (2012) Correlation between hippocampal levels of neural, epithelial, and inducible NOS and spatial learning skills in rats. Behav Brain Res 235(2):326–333CrossRefGoogle Scholar
  36. 36.
    Hassan HA, Yousef MI (2009) Mitigating effects of antioxidant properties of black berry juice on sodium fluoride induced hepatotoxicity and oxidative stress in rats. Food Chem Toxicol 47(9):2332–2337PubMedCrossRefGoogle Scholar
  37. 37.
    Mittal M, Flora SJ (2006) Effects of individual and combined exposure to sodium arsenite and sodium fluoride on tissue oxidative stress, arsenic, and fluoride levels in male mice. Chem Biol Interact 162(2):128–139PubMedCrossRefGoogle Scholar
  38. 38.
    Boeckers TM (2006) The postsynaptic density. Cell Tissu Res 326(2):409–422CrossRefGoogle Scholar
  39. 39.
    Holly JC, Ann EF, Seth GN et al (2008) Opposing effects of PSD-93 and PSD-95 on long-term potentiation and spike timing-dependent plasticity. J Physiol 586(24):5885–5900CrossRefGoogle Scholar
  40. 40.
    Lin CS, Tao PL, Jong YJ et al (2009) Prenatal morphine alters the synaptic complex of postsynaptic density 95 with N-methyl-aspartate receptor subunit in hippocampal CA1 subregion of rat offspring leading to long-term cognitive deficits. Neuroscience 158(4):1326–1337PubMedCrossRefGoogle Scholar
  41. 41.
    Du CP, Gao J, Tai JM et al (2009) Increased tyrosine phosphorylation of PSD-95 by Src family kinases after brain ischemia. J Biochem 417(1):277–285CrossRefGoogle Scholar
  42. 42.
    Xu WF (2011) PSD-95-like membrane associated guanylate kinases (PSDMAGUKs) and synaptic plasticity. Curr Opin Neurobiol 21(2):306–312PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.College of Chemistry and Life ScienceZhejiang Normal UniversityJinhuaPeople’s Republic of China

Personalised recommendations