Increased Tau Phosphorylation and Beta Amyloid in the Hippocampus of Mouse Pups by Early Life Lead Exposure


The aim of this study was to investigate the effects of maternal lead exposure on the learning and memory ability and expression of tau protein phosphorylation (P-tau) and beta amyloid protein (Aβ) in hippocampus of mice offspring. Pb exposure initiated from beginning of gestation to weaning. Pb acetate administered in drinking solutions was dissolved in distilled deionized water at the concentrations of 0.1%, 0.5% and 1% groups. On the 21th of postnatal day, the learning and memory ability of the mouse pups was tested by Water Maze test and the Pb levels in blood and hippocampus of the offspring were also determined. The expression of P-tau and AP in hippocampus was measured by immunohistochemistry and Western blotting. The Pb levels in blood and hippocampus of all exposure groups were significantly higher than that of the control group (P<0.05). In Water Maze test, the performances of 0.5% and 1% groups were worse than that of the control group (P<0.05). The expression of P-tau and Aβ was increased in Pb exposed groups than that of the control group (P<0.05). Tau hyper-phosphorylation and Aβ increase in the hippocampus of pups may contribute to the impairment of learning and memory associated with maternal Pb exposure.


  1. 1.

    Abbott, R. D., White, L. R., Ross, G. W., Petrovitch, H., Masaki, K. H., Snowdon, D. A., Curb, J. D. (1998) Height as a marker of childhood development and late-life cognitive function: The Honolulu-Asia Aging Study. Pediatrics 102, 602–609.

    CAS  Article  Google Scholar 

  2. 2.

    Alonso Adel, C., Li, B., Grundke-Iqbal, I., Iqbal, K. (2006) Polymerization of hyperphosphorylated tau into filaments eliminates its inhibitory activity. Proc. Natl. Acad. Sci. U.S.A. 103, 8864–8869.

    Article  Google Scholar 

  3. 3.

    Basha, M. R., Wei, W., Brydie, M., Razmiafshari, M., Zawia, N. H. (2003) Lead induced developmental perturbations in hippocampal Spl DNA-binding are prevented by zinc supplementation. Int. J. Dev. Neurosci. 21, 1–12.

    CAS  Article  Google Scholar 

  4. 4.

    Bertram, L., Tanzi, R. E. (2004) Alzheimer’s disease: One disorder, too many genes? Hum. Mol Genet. 13, R135–R141.

    CAS  Article  Google Scholar 

  5. 5.

    Bradbury, M. W., Deane, R. (1993) Permeability of the blood-brain barrier to lead. Neurotoxicology 14, 131–136.

    CAS  PubMed  Google Scholar 

  6. 6.

    Canfield, R. L., Henderson, C. R. Jr., Cory-Slechta, D. A., Cox, C., Jusko, T. A., Lanphear, B. P. (2003) Intellectual impairment in children with blood lead concentrations below 10 microg per deciliter. N. Engl. J. Med. 348, 1517–1526.

    CAS  Article  Google Scholar 

  7. 7.

    Cao, X. J., Huang, S. H., Wang, M., Chen, J. T., Ruan, D. Y. (2008) S-adenosyl-L-methionine improves impaired hippocampal long-term potentiation and water maze performance induced by developmental lead exposure in rats. Eur. J. Pharmacol. 595, 30–34.

    CAS  Article  Google Scholar 

  8. 8.

    Carpenter, D. O., Matthews, M. R., Parsons, P. J., Hori, N. (1994) Long-term potentiation in the piriform cortex is blocked by lead. Cell Mol. Neurobiol. Dec. 14, 723–733.

    CAS  Article  Google Scholar 

  9. 9.

    Cory-Slechta, D. A., Flaugher, C. L., Evans, S. B., Pokora, M. J., Greenamyre, J. T. (1997) Susceptibility of adult rats to lead-induced changes in NMDA receptor complex function. Neurotoxicol. Teratol. 19, 517–530.

    CAS  Article  Google Scholar 

  10. 10.

    Gardella, C. (2001) Lead exposure in pregnancy: a review of the literature and argument for routine prenatal screening. Obstet. Gynecol. Surv. 56, 231–238.

    CAS  Article  Google Scholar 

  11. 11.

    Gatz, M., Fratiglioni, L., Johansson, B., Berg, S., Mortimer, J. A., Reynolds, C. A., Fiske, A., Pedersen, N. L. (2005) Complete ascertainment of dementia in the Swedish Twin Registry: The HARMONY study. Neurobiol. Aging 26, 439–447.

    Article  Google Scholar 

  12. 12.

    Gilbert, M. E., Lasley, S. M. (2007) Developmental lead (Pb) exposure reduces the ability of the NMDA antagonist MK-801 to suppress long-term potentiation (LTP) in the rat dentate gyrus, in vivo. Neurotoxicol. Teratol. 29, 385–393.

    CAS  Article  Google Scholar 

  13. 13.

    Gorell, J. M., Rybicki, B. A., Cole Johnson, C., Peterson, E. L. (1999) Occupational metal exposures and the risk of Parkinson’sdisease. Neuroepidemiology 18, 303–308.

    CAS  Article  Google Scholar 

  14. 14.

    Haraguchi, T., Ishizu, H., Takehisa, Y., Kawai, K., Yokota, O., Terada, S., Tsuchiya, K., Ikeda, K., Morita, K., Horike, T., Kira, S., Kuroda, S. (2001) Lead content of brain tissue in diffuse neurofibrillary tangles with calcification (DNTC): The possibility of lead neurotoxicity. Neuro. Report. 12. 3887–3890.

    CAS  Google Scholar 

  15. 15.

    Hrnkova, M., Zilka, N., Minichova, Z., Koson, P., Novak, M. (2007) Neurodegeneration caused by expression of human truncated tau leads to progressive neurobehavioural impairment in transgenic rats. Brain Res. 1130, 206–213.

    CAS  Article  Google Scholar 

  16. 16.

    Kamel, F., Umbach, D. M., Munsat, T. L., Shefner, J. M., Hu, H., Sandler, D. P. (2002) Lead exposure and amyotrophic lateral sclerosis. Epidemiology 13, 311–319.

    Article  Google Scholar 

  17. 17.

    Mendola, P., Selevan, S. G., Gutter, S., Rice, D. (2002) Environmental factors associated with the spectrum of neurodevelopmental deficits. Ment. Retard Dev. Disabil. Res. Rev. 8, 188–197.

    Article  Google Scholar 

  18. 18.

    Munoz, D. G., Feldman, H. (2000) Causes of Alzheimer’s disease. CMAJ 162, 65–72.

    CAS  PubMed  PubMed Central  Google Scholar 

  19. 19.

    Niklowitz, W. J., Mandybur, T. I. (1975) Neurofibrillary changes following childhood lead encephalopathy. J. Neuropathol. Exp. Neurol. 34, 445–455.

    CAS  Article  Google Scholar 

  20. 20.

    Plusquellec, P., Muckle, G., Dewailly, E., Ayotte, P., Jacobson, S. W., Jacobson, J. L. (2007) The relation of low-level prenatal lead exposure to behavioral indicators of attention in Inuit infants in Arctic Quebec. Neurotoxicol. Teratol. 29, 527–537.

    CAS  Article  Google Scholar 

  21. 21.

    Qian, Y., Harris, E. D., Zheng, Y., Tiffany-Castiglioni, E. (2000) Lead targets GRP78, a molecular chaperone, in C6 rat glioma cells. Toxicol. Appl. Pharmacol. 163, 260–266.

    CAS  Article  Google Scholar 

  22. 22.

    Reddy, G. R., Zawia, N. H. (2000) Lead exposure alters Egr-1 DNA binding in the neonatal rat brain. Int. J. Dev. Neurosci. 18, 791–795.

    CAS  Article  Google Scholar 

  23. 23.

    Salanki, J., Györi, J., Carpenter, D. O. (1994) Action of lead on glutamate-activated chloride currents in Helix pomatia L. neurons. Cell Mol. Neurobiol. 14, 755–768.

    CAS  Article  Google Scholar 

  24. 24.

    Selkoe, D. J. (2001) Alzheimer’s disease: genes, proteins, and therapy. Physiol. Rev. 81, 741–766.

    CAS  Article  Google Scholar 

  25. 25.

    Sorra, K. E., Harris, K. M. (2000) Overview on the structure, composition, function, development, and plasticity of hippocampal dendritic spines. Hippocampus 10, 501–511.

    CAS  Article  Google Scholar 

  26. 26.

    Sorra, K. E., Harris, K. M. (1998) Stability in synapse number and size at 2 h after long-term potentiation in hippocampal area CA1. J. Neurosci. 18, 658–671.

    CAS  Article  Google Scholar 

  27. 27.

    Stewart, W. F., Schwartz, B. S., Davatzikos, C., Shen, D., Liu, D., Wu, X., Todd, A. C., Shi, W., Bassett, S., Youssem, D. (2006) Past adult lead exposure is linked to neurodegeneration measured by brain MRI. Neurology 66, 1476–1484.

    CAS  Article  Google Scholar 

  28. 28.

    Stewart, W. F., Schwartz, B. S., Simon, D., Kelsey, K., Todd, A. C. (2002) ApoE genotype, past adult lead exposure, and neurobehavioral function. Environ. Health. Perspect. 110, 501–505.

    CAS  Article  Google Scholar 

  29. 29.

    Suh, Y H., Checler, F. (2002) Amyloid precursor protein, presenilins, and alpha-synuclein: Molecular pathogenesis and pharmacological applications in Alzheimer’s disease. Pharmacol. Rev. 54, 469–525.

    CAS  Article  Google Scholar 

  30. 30.

    Suresh, C., Dennis, A. O., Heinz, J., Vemuri, M. C., Chetty, C. S. (2006) Melatonin protection against lead-induced changes in human neruoblastoma cell cultures. Int. J. Toxicol. 25, 459–464.

    CAS  Article  Google Scholar 

  31. 31.

    Tong, S., McMichael, A. J., Baghurst, P. A. (2000) Interactions between environmental lead exposure and sociodemographic factors on cognitive development. Arch. Environ. Health 55, 330–335.

    CAS  Article  Google Scholar 

  32. 32.

    Zhu, Z. W., Yang, R. L., Dong, G. J., Zhao, Z. Y (2005) Study on the neurotoxic effects of low-level lead exposure in rats. J. Zhejiang Univ. Sci. B. 6, 686–692.

    Article  Google Scholar 

Download references

Author information



Corresponding author

Correspondence to W. J. Li.

Rights and permissions

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

Reprints and Permissions

About this article

Cite this article

Li, N., Yu, Z.L., Wang, L. et al. Increased Tau Phosphorylation and Beta Amyloid in the Hippocampus of Mouse Pups by Early Life Lead Exposure. BIOLOGIA FUTURA 61, 123–134 (2010).

Download citation


  • Lead (Pb)
  • tau phosphorylation
  • beta amyloid
  • neurotoxicity
  • learning and memory