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  • 1 Zhengzhou University College of Public Health Zhengzhou 450001 China
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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 21 th 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 Aβ 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.

  • 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.

    Curb J. D. , 'Height as a marker of childhood development and late-life cognitive function: The Honolulu-Asia Aging Study ' (1998 ) 102 Pediatrics : 602 -609.

    • Search Google Scholar
  • 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.

    Iqbal K. , 'Polymerization of hyperphosphorylated tau into filaments eliminates its inhibitory activity ' (2006 ) 103 Proc. Natl. Acad. Sci. U.S.A. : 8864 -8869.

    • Search Google Scholar
  • Basha, M. R., Wei, W., Brydie, M., Razmiafshari, M., Zawia, N. H. (2003) Lead induced developmental perturbations in hippocampal Sp1 DNA-binding are prevented by zinc supplementation. Int. J. Dev. Neurosci. 21 , 1–12.

    Zawia N. H. , 'Lead induced developmental perturbations in hippocampal Sp1 DNA-binding are prevented by zinc supplementation ' (2003 ) 21 Int. J. Dev. Neurosci. : 1 -12.

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

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

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

    Deane R. , 'Permeability of the blood-brain barrier to lead ' (1993 ) 14 Neurotoxicology : 131 -136.

    • Search Google Scholar
  • 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.

    Lanphear B. P. , 'Intellectual impairment in children with blood lead concentrations below 10 microg per deciliter ' (2003 ) 348 N. Engl. J. Med. : 1517 -1526.

    • Search Google Scholar
  • 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.

    Ruan D. Y. , 'S-adenosyl-L-methionine improves impaired hippocampal long-term potentiation and water maze performance induced by developmental lead exposure in rats ' (2008 ) 595 Eur. J. Pharmacol. : 30 -34.

    • Search Google Scholar
  • 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.

    Hori N. , 'Long-term potentiation in the piriform cortex is blocked by lead ' (1994 ) 14 Cell Mol. Neurobiol. Dec. : 723 -733.

    • Search Google Scholar
  • 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.

    Greenamyre J. T. , 'Susceptibility of adult rats to lead-induced changes in NMDA receptor complex function ' (1997 ) 19 Neurotoxicol. Teratol. : 517 -530.

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

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

    • Search Google Scholar
  • 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.

    Pedersen N. L. , 'Complete ascertainment of dementia in the Swedish Twin Registry: The HARMONY study ' (2005 ) 26 Neurobiol. Aging : 439 -447.

    • Search Google Scholar
  • 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.

    Lasley S. M. , '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 ' (2007 ) 29 Neurotoxicol. Teratol. : 385 -393.

    • Search Google Scholar
  • 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.

    Peterson E. L. , 'Occupational metal exposures and the risk of Parkinson’sdisease ' (1999 ) 18 Neuroepidemiology : 303 -308.

    • Search Google Scholar
  • 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.

    Kuroda S. , 'Lead content of brain tissue in diffuse neurofibrillary tangles with calcification (DNTC): The possibility of lead neurotoxicity ' (2001 ) 12 Neuro. Report. : 3887 -3890.

    • Search Google Scholar
  • 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.

    Novak M. , 'Neurodegeneration caused by expression of human truncated tau leads to progressive neurobehavioural impairment in transgenic rats ' (2007 ) 1130 Brain Res. : 206 -213.

    • Search Google Scholar
  • 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.

    Sandler D. P. , 'Lead exposure and amyotrophic lateral sclerosis ' (2002 ) 13 Epidemiology : 311 -319.

    • Search Google Scholar
  • 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.

    Rice D. , 'Environmental factors associated with the spectrum of neurodevelopmental deficits ' (2002 ) 8 Ment. Retard. Dev. Disabil. Res. Rev. : 188 -197.

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

    Feldman H. , 'Causes of Alzheimer’s disease ' (2000 ) 162 CMAJ : 65 -72.

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

    Mandybur T. I. , 'Neurofibrillary changes following childhood lead encephalopathy ' (1975 ) 34 J. Neuropathol. Exp. Neurol. : 445 -455.

    • Search Google Scholar
  • 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.

    Jacobson J. L. , 'The relation of low-level prenatal lead exposure to behavioral indicators of attention in Inuit infants in Arctic Quebec ' (2007 ) 29 Neurotoxicol. Teratol. : 527 -537.

    • Search Google Scholar
  • 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.

    Tiffany-Castiglioni E. , 'Lead targets GRP78, a molecular chaperone, in C6 rat glioma cells ' (2000 ) 163 Toxicol. Appl. Pharmacol. : 260 -266.

    • Search Google Scholar
  • 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.

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

    • Search Google Scholar
  • Salánki, 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.

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

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

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

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

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

    • Search Google Scholar
  • 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.

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

    • Search Google Scholar
  • 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.

    Youssem D. , 'Past adult lead exposure is linked to neurodegeneration measured by brain MRI ' (2006 ) 66 Neurology : 1476 -1484.

    • Search Google Scholar
  • 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.

    Todd A. C. , 'ApoE genotype, past adult lead exposure, and neurobehavioral function ' (2002 ) 110 Environ. Health. Perspect. : 501 -505.

    • Search Google Scholar
  • 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.

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

    • Search Google Scholar
  • 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.

    Chetty C. S. , 'Melatonin protection against lead-induced changes in human neruoblastoma cell cultures ' (2006 ) 25 Int. J. Toxicol. : 459 -464.

    • Search Google Scholar
  • 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.

    Baghurst P. A. , 'Interactions between environmental lead exposure and sociodemographic factors on cognitive development ' (2000 ) 55 Arch. Environ. Health : 330 -335.

    • Search Google Scholar
  • 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.

    Zhao Z. Y. , 'Study on the neurotoxic effects of low-level lead exposure in rats ' (2005 ) 6 J. Zhejiang Univ. Sci. B. : 686 -692.

    • Search Google Scholar