Abstract
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.
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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.
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.
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.
Bertram, L., Tanzi, R. E. (2004) Alzheimer’s disease: One disorder, too many genes? Hum. Mol Genet. 13, R135–R141.
Bradbury, M. W., Deane, R. (1993) Permeability of the blood-brain barrier to lead. Neurotoxicology 14, 131–136.
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.
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.
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.
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.
Gardella, C. (2001) Lead exposure in pregnancy: a review of the literature and argument for routine prenatal screening. Obstet. Gynecol. Surv. 56, 231–238.
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.
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.
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.
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.
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.
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.
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.
Munoz, D. G., Feldman, H. (2000) Causes of Alzheimer’s disease. CMAJ 162, 65–72.
Niklowitz, W. J., Mandybur, T. I. (1975) Neurofibrillary changes following childhood lead encephalopathy. J. Neuropathol. Exp. Neurol. 34, 445–455.
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.
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.
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.
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.
Selkoe, D. J. (2001) Alzheimer’s disease: genes, proteins, and therapy. Physiol. Rev. 81, 741–766.
Sorra, K. E., Harris, K. M. (2000) Overview on the structure, composition, function, development, and plasticity of hippocampal dendritic spines. Hippocampus 10, 501–511.
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.
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.
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.
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.
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.
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.
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.
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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). https://doi.org/10.1556/ABiol.61.2010.2.1
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DOI: https://doi.org/10.1556/ABiol.61.2010.2.1