Skip to main content

Advertisement

Log in

Proteomic Analysis of Hippocampus in Offspring Male Mice Exposed to Fluoride and Lead

  • Published:
Biological Trace Element Research Aims and scope Submit manuscript

Abstract

Fluoride and lead are two common pollutants in the environment. Previous investigations have found that high fluoride exposure can increase the lead burden. In this experiment, in order to study on the molecular mechanisms of central neural system injury induced by the above two elements, differently expressed protein spots in hippocampus of male mice treated with 150 mg sodium fluoride/L and/or 300 mg lead acetate/L in their drinking water were detected by two-dimensional electrophoresis (2-DE) and mass spectrometry (MS). The behavior tests showed that 56 days of fluoride and lead administration significantly reduced the vertical activity and lowered the memory ability of mice. In addition, results of 2-DE and MS revealed that nine spots demonstrated above a twofold change in the same trend in all treatment groups, which were mainly related with (1) energy metabolism, (2) cell stress response/chaperones, (3) cytoskeleton development, (4) protein metabolism, and (5) cell surface signal transduction. The findings could provide potential biomarkers for lesion in nervous system induced by fluoride and lead exposure.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Adebayo OL, Shallie PD, Salau BA et al (2013) Comparative study on the influence of fluoride on lipid peroxidation and antioxidants levels in the different brain regions of well-fed and protein undernourished rats. J Trace Elem Med Biol 27(4):370–374

    Article  CAS  PubMed  Google Scholar 

  2. Zhang J, Zhu WJ, Xu XH et al (2011) Effect of fluoride on calcium ion concentration and expression of nuclear transcription factor kappa-B r65 in rat hippocampus. Exp Toxicol Pathol 67(5):407–411

    Article  Google Scholar 

  3. Liu YJ, Guan ZZ, Gao Q et al (2011) Increased level of apoptosis in rat brains and SH-SY5Y cells exposed to excessive fluoride—a mechanism connected with activating JNK phosphorylation. Toxicol Lett 204(2–3):183–189

    Article  CAS  PubMed  Google Scholar 

  4. Zhou BH, Wang HW, Wang JM et al (2007) Effects of malnutrition and supplemented nutrition on non-specific immune function changes induced by fluoride in rabbits. Fluoride 40(3):169–177

    CAS  Google Scholar 

  5. Xu H, Hu LS, Chang M et al (2005) Proteomic analysis of kidney in fluoride-treated rat. Toxicol Lett 160(1):69–75

    Article  CAS  PubMed  Google Scholar 

  6. Liu HT, Niu RY, Wang JM et al (2008) Changes caused by fluoride and lead in energy metabolic enzyme activities in the reproductive system of male offspring rats. Fluoride 41(3):184–191

    CAS  Google Scholar 

  7. Bouaziz H, Ben Amara I, Essefi M et al (2010) Fluoride-induced brain damages in suckling mice. Pestic Biochem Physiol 96(1):24–29

    Article  CAS  Google Scholar 

  8. Ding Y, Gao Y, Sun H et al (2011) The relationships between low levels of urine fluoride on children's intelligence, dental fluorosis in endemic fluorosis areas in Hulunbuir, Inner Mongolia, China. J Hazard Mater 186(2–3):1942–1946

    Article  CAS  PubMed  Google Scholar 

  9. Wang SX, Wang ZH, Cheng XT et al (2007) Arsenic and fluoride exposure in drinking water: children's IQ and growth in Shanyin county, Shanxi province, China. Environ Health Perspect 115(4):643–647

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  10. Eswar P, Nagesh L, Devarajc C (2011) Intelligence quotients of 12–14 years old school children in a high and a low fluoride village in India. Fluoride 44(3):168–172

    CAS  Google Scholar 

  11. Saxena S, Sahay A, Goel P (2012) Effect of fluoride exposure on the intelligence of school children in Madhya Pradesh, India. J Neurosci Rural Pract 3(2):144–149

    Article  PubMed Central  PubMed  Google Scholar 

  12. Trivedi M, Sangai N, Patel R et al (2012) Assessment of groundwater quality with special reference to fluoride and its impact on IQ of schoolchildren in six villages of the Mundra region, Kachchh, Gujarat, India. Fluoride 45(4):377–383

    CAS  Google Scholar 

  13. Shivaprakash PK, Ohri K, Noorani H (2011) Relation between dental fluorosis and intelligence quotient in school children of Bagalkot district. J Indian Soc Pedod Prev Dent 29(2):117–120

    Article  CAS  PubMed  Google Scholar 

  14. Poureslami HR, Horri A, Garrusib B (2011) IQ of children age 7–9 in a high and a low F water city in Iran. Fluoride 44(3):163–167

    CAS  Google Scholar 

  15. Seraj B, Shahrabi M, Shadfar M et al (2012) Effect of high water fluoride concentration on the intellectual development of children in makoo/iran. J Dent (Tehran) 9(3):221–229

    CAS  Google Scholar 

  16. Rocha-Amador D, Navarro ME, Carrizales L et al (2007) Decreased intelligence in children and exposure to fluoride and arsenic in drinking water. Cad Saude Publ 23(Suppl 4):579–587

    Article  Google Scholar 

  17. Whishaw IQ, Haun F, Kolb BL (1999) Analysis of behavior in laboratory rodents. IN: Windhorst U, Johansson H, editors. Modern techniques in neuroscience research. Secaucus: Springer; 1243–1244

  18. Niu RY, Sun ZL, Wang JM et al (2008) Effects of fluoride and lead on locomotor behavior and expression of Nissl body in brain of adult rats. Fluoride 41(4):276–282

    CAS  Google Scholar 

  19. Ekambaram P, Paul V (2001) Calcium preventing locomotor behavioral and dental toxicities of fluoride by decreasing serum fluoride level in rats. Environ Toxicol Pharmacol 9(4):141–146

    Article  CAS  PubMed  Google Scholar 

  20. Balaji B, Kumar EP, Kumar A (2012) Evaluation of standardized Bacopa monniera extract in sodium fluoride-induced behavioural, biochemical, and histopathological alterations in mice. Toxicol Ind Health. doi:10.1177/0748233712468018

    Google Scholar 

  21. Jiang S, Su J, Yao S et al (2014) Fluoride and arsenic exposure impairs learning and memory and decreases mGluR5 expression in the hippocampus and cortex in rats. PLoS One 9(4):e96041

    Article  PubMed Central  PubMed  Google Scholar 

  22. Niu RY, Sun ZL, Cheng ZT et al (2008) Effects of fluoride and lead on n-methyl-d-aspartate receptor 1 expression in the hippocampus of offspring rat pups. Fluoride 41(2):101–110

    CAS  Google Scholar 

  23. Gao Q, Liu YJ, Guan ZZ (2008) Oxidative stress might be a mechanism connected with the decreased alpha 7 nicotinic receptor influenced by high-concentration of fluoride in SH-SY5Y neuroblastoma cells. Toxicol In Vitro 22(4):837–843

    Article  CAS  PubMed  Google Scholar 

  24. Inkielewicz-Stepniak I, Czarnowski W (2010) Oxidative stress parameters in rats exposed to fluoride and caffeine. Food Chem Toxicol 48(6):1607–1611

    Article  CAS  PubMed  Google Scholar 

  25. Coplan MJ, Patch SC, Masters RD et al (2007) Confirmation of and explanations for elevated blood lead and other disorders in children exposed to water disinfection and fluoridation chemicals. Neurotoxicology 28(5):1032–1042

    Article  CAS  PubMed  Google Scholar 

  26. Masters RD, Coplan MJ, Hone BT et al (2000) Association of silicofluoride treated water with elevated blood lead. Neurotoxicology 21(6):1091–1100

    CAS  PubMed  Google Scholar 

  27. Zhai Y, Dong J, Cao XZ et al (2006) Epidemiological investigation about the relation between blood lead level and high fluorine drinking water in children. Child Health Care China 21(8):1088–1090 [in Chinese]

    Google Scholar 

  28. Sawan RM, Leite GA, Saraiva MC et al (2010) Fluoride increases lead concentrations in whole blood and in calcified tissues from lead-exposed rats. Toxicology 271(1–2):21–26

    Article  CAS  PubMed  Google Scholar 

  29. Bevins RA, Besheer J (2006) Object recognition in rats and mice: a one-trial non-matching-to-sample learning task to study ‘recognition memory’. Nat Protoc 1(3):1306–1311

    Article  PubMed  Google Scholar 

  30. Ge Y, Niu R, Zhang J et al (2011) Proteomic analysis of brain proteins of rats exposed to high fluoride and low iodine. Arch Toxicol 85(1):27–33

    Article  CAS  PubMed  Google Scholar 

  31. Okajima K, Korotchkina LG, Prasad C et al (2008) Mutations of the E1beta subunit gene (PDHB) in four families with pyruvate dehydrogenase deficiency. Mol Genet Metab 93(4):371–380

    Article  CAS  PubMed  Google Scholar 

  32. Patel MS, Korotchkina LG (2006) Regulation of the pyruvate dehydrogenase complex. Biochem Soc Trans 34:217–222

    Article  CAS  PubMed  Google Scholar 

  33. Kerr DS, Schmotzer C (2004) Variability of human pyruvate dehydrogenase complex deficiency. In: Patel MS, Jordan F (eds) Thiamine: catalytic mechanisms and role in normal and disease states. Marcel Dekker, New York, pp 471–483

    Google Scholar 

  34. Lissens W, De Meirleir L, Seneca S et al (2000) Mutations in the X-linked pyruvate dehydrogenase (E1) alpha subunit gene (PDHA1) in patients with a pyruvate dehydrogenase complex deficiency. Hum Mutat 15(3):209–219

    Article  CAS  PubMed  Google Scholar 

  35. Korotchkina LG, Ciszak EM, Patel MS (2004) Function of several critical amino acids in human pyruvate dehydrogenase revealed by its structure. Arch Biochem Biophys 429(2):171–179

    Article  CAS  PubMed  Google Scholar 

  36. Soole KL, Menz RI (1995) Functional molecular aspects of the NADH dehydrogenases of plant mitochondria. J Bioenerg Biomembr 27(4):397–406

    Article  CAS  PubMed  Google Scholar 

  37. Rupik W, Jasik K, Bembenek J et al (2011) The expression patterns of heat shock genes and proteins and their role during vertebrate's development. Comp Biochem Physiol A 159(4):349–366

    Article  Google Scholar 

  38. Heikkila JJ (2010) Heat shock protein gene expression and function in amphibian model systems. Comp Biochem Physiol A 156(1):19–33

    Article  Google Scholar 

  39. Mayer MP, Bukau B (2005) Hsp70 chaperones: cellular functions and molecular mechanism. Cell Mol Life Sci 62(6):670–684

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  40. Elicker KS, Hutson LD (2007) Genome-wide analysis and expression profiling of the small heat shock proteins in zebrafish. Gene 403(1–2):60–69

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  41. Christensen JH, Nielsen MN, Hansen J et al (2010) Inactivation of the hereditary spastic paraplegia-associated Hspd1 gene encoding the Hsp60 chaperone results in early embryonic lethality in mice. Cell Stress Chaperones 15(6):851–863

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  42. Samali A, Cai J, Zhivotovsky B et al (1999) Presence of a pre-apoptotic complex of pro-caspase-3, Hsp60 and Hsp10 in the mitochondrial fraction of Jurkat cells. EMBO J 18(8):2040–2048

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  43. Quinn CC, Gray GE, Hockfield S (1999) A family of proteins implicated in axon guidance and outgrowth. J Neurobiol 41(1):158–164

    Article  CAS  PubMed  Google Scholar 

  44. Wang LH, Strittmatter SM (1996) A family of rat CRMP genes is differentially expressed in the nervous system. J Neurosci 16(19):6197–6207

    CAS  PubMed  Google Scholar 

  45. Voas MG, Lyons DA, Naylor SG et al (2007) AlphaII-spectrin is essential for assembly of the nodes of Ranvier in myelinated axons. Curr Biol 17(6):562–568

    Article  CAS  PubMed  Google Scholar 

  46. Zhang M, Huang K, Zhang Z et al (2011) Proteome alterations of cortex and hippocampus tissues in mice subjected to vitamin A depletion. J Nutr Biochem 22(11):1003–1008

    Article  CAS  PubMed  Google Scholar 

  47. Chen A, Liao WP, Lu Q et al (2007) Upregulation of dihydropyrimidinase-related protein 2, spectrin α II chain, heat shock cognate protein 70 pseudogene 1 and tropomodulin 2 after focal cerebral ischemia in rats—a proteomics approach. Neurochem Int 50(7–8):1078–1086

    Article  CAS  PubMed  Google Scholar 

  48. Matsuda-Matsumoto H, Iwazaki T, Kashem MA et al (2007) Differential protein expression profiles in the hippocampus of human alcoholics. Neurochem Int 51(6–7):370–376

    Article  CAS  PubMed  Google Scholar 

  49. Indraswari F, Wong PT, Yap E et al (2009) Upregulation of Dpysl2 and Spna2 gene expression in the rat brain after ischemic stroke. Neurochem Int 55(4):235–242

    Article  CAS  PubMed  Google Scholar 

  50. Valdez-Jiménez L, Soria Fregozo C, Miranda Beltrán ML et al (2011) Effects of the fluoride on the central nervous system. Neurologia 26(5):297–300

    Article  PubMed  Google Scholar 

  51. Thornhill PB, Cohn JB, Stanford WL et al (2008) The adaptor protein Grb2 regulates cell surface Fas ligand in Schwann cells. Biochem Biophys Res Commun 376(2):341–346

    Article  CAS  PubMed  Google Scholar 

  52. Anteby EY, Ayesh S, Shochina M et al (2005) Growth factor receptor-protein bound 2 (GRB2) up-regulation in the placenta in preeclampsia implies a possible role for ras-signalling. J Obstet Gynecol Reprod Biol 118(2):174–181

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This research was supported by the China National Natural Science Foundation (Grant Nos. 31101869, 31201965, and 31172376), Shanxi Province Natural Science Foundation (Grant No. 2012021027–5), and Program for the Top Young Academic Leaders of Higher Learning Institutions of Shanxi.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Zilong Sun or Jundong Wang.

Additional information

Ruiyan Niu and Shuangling Liu contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Niu, R., Liu, S., Wang, J. et al. Proteomic Analysis of Hippocampus in Offspring Male Mice Exposed to Fluoride and Lead. Biol Trace Elem Res 162, 227–233 (2014). https://doi.org/10.1007/s12011-014-0117-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12011-014-0117-2

Keywords

Navigation