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Journal of Zhejiang University SCIENCE B 2005 Vol.6 No.7 P.686-692

http://doi.org/10.1631/jzus.2005.B0686


Study on the neurotoxic effects of low-level lead exposure in rats


Author(s):  ZHU Zhi-wei, YANG Ru-Lai, DONG Gui-juan, ZHAO Zheng-yan

Affiliation(s):  Affiliated Children’ more

Corresponding email(s):   zhaozy@zju.edu.cn

Key Words:  Lead exposure, Rat pups, Nitric oxide synthase (NOS), Fluorescence, Hippocampus, mRNA, Retro-translation (RT-PCR), N-methyl-D-aspartate receptor (NMDAR)


ZHU Zhi-wei, YANG Ru-Lai, DONG Gui-juan, ZHAO Zheng-yan. Study on the neurotoxic effects of low-level lead exposure in rats[J]. Journal of Zhejiang University Science B, 2005, 6(7): 686-692.

@article{title="Study on the neurotoxic effects of low-level lead exposure in rats",
author="ZHU Zhi-wei, YANG Ru-Lai, DONG Gui-juan, ZHAO Zheng-yan",
journal="Journal of Zhejiang University Science B",
volume="6",
number="7",
pages="686-692",
year="2005",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.2005.B0686"
}

%0 Journal Article
%T Study on the neurotoxic effects of low-level lead exposure in rats
%A ZHU Zhi-wei
%A YANG Ru-Lai
%A DONG Gui-juan
%A ZHAO Zheng-yan
%J Journal of Zhejiang University SCIENCE B
%V 6
%N 7
%P 686-692
%@ 1673-1581
%D 2005
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.2005.B0686

TY - JOUR
T1 - Study on the neurotoxic effects of low-level lead exposure in rats
A1 - ZHU Zhi-wei
A1 - YANG Ru-Lai
A1 - DONG Gui-juan
A1 - ZHAO Zheng-yan
J0 - Journal of Zhejiang University Science B
VL - 6
IS - 7
SP - 686
EP - 692
%@ 1673-1581
Y1 - 2005
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.2005.B0686


Abstract: 
Objective: To investigate effects of developmental lead exposure on nitric oxide synthase (NOS) activity in different brain regions and on N-methyl-D-aspartate (NMDA) receptor mRNA expression in the hippocampus of rats. On the basis of these observations, we explored possible mechanisms by which lead exposure leads to impaired learning and memorizing abilities in children. Methods: A series of rat animal models exposed to low levels of lead during the developing period was established (drinking water containing 0.025%, 0.05% and 0.075% lead acetate). NOS activities in the hippocampus, the cerebral cortex, the cerebellum and the brain stem were determined with fluorescence measurement and levels of mRNA expression of the NMDA receptor 2A (NR2A) subunit and NMDA receptor 2B (NR2B) subunit in the rat hippocampus were measured with retro-translation (RT-PCR). Results: There were no differences in the body weight of rat pups between any of the groups at any given time (P>0.05). The blood lead level of Pb-exposed rat pups showed a systematic pattern of change: at 14 d of age, it was lower than that at 7 d of age, then rising to the peak level at 21 d and finally falling to lower levels at 28 d. The hippocampal NOS activities of lead-exposed groups were all lower than that of the control group on the 21st and 28th day (P<0.01). NOS activities in the cerebellum of lead-exposed groups were all lower than that of the control group on the 21st and 28th day (P<0.001) and the NOS activity of the 0.025% group was significantly lower than that of the 0.05% and 0.075% groups on the 28th day (P<0.05). NOS activity in the cerebral cortex of the 0.075% group was significantly lower than that of the control, 0.025% and 0.05% groups on the four day spans (P<0.001). There was no significant difference of NOS activity in the brain stem between any lead-exposed group and the control group on the four day spans. In the 0.05% and the 0.075% groups, the level of NR2A mRNA expression was higher than that in the control group at 7 d and 14 d of age (P<0.05). In the 0.025% group, the level of NR2A was found to be higher than that in the control group at 7 d of age only (P<0.05). No significant differences were found for the levels of NR2B mRNA expression between any of the groups at any given time. Conclusions: NOS activity in the hippocampus, the cerebral cortex and the cerebellum are inhibited by lead exposure. The degree of the inhibitory effect depends on the time span of exposure and the lead concentration. Developmental low-level lead exposure was found to raise the level of NR2A mRNA expression in the hippocampus of rats. Developmental low-level lead exposure does not affect the level of NR2B mRNA expression in the hippocampus.

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Reference

[1] Altmann, L., Weinsberg, F., Sveinsson, K., 1993. Impairment of long-term potentiation and learning following chronic lead exposure. Toxicol Lett, 66(1):105-112.

[2] Bellinger, D., Sloman, J., Leviton, A., Rabinowitz, M., Needleman, H.L., Watemaux, C., 1991. Low-level lead exposure and children’s cognitive function in the preschool years. Pediatrics, 87:219-227.

[3] Chetty, C.S., Reddy, G.R., Murthy, K.S., Johnson, J., Sajwan, K., Desaiah, D., 2001. Perinatal lead exposure alters the expression of neuronal nitric oxide synthase in rat brain. Int. J. Toxicol, 20(3):113-120.

[4] Collingridge, G.L., Singer, W., 1990. Excitatory amino acid receptors and synaptic plasticity. TIPS, 11:290-296.

[5] Guilarte, T.R., McGlothan, J.L., 1998. Hippocampal NMDA receptor mRNA undergoes subunit specific changes during developmental lead exposure. Brain Research, 790:98-107.

[6] Han, J.S., 1993. Neuro-Science Compendium. Beijing Medical University and Xiehe Medical University United Publishing Company, Beijing, China, p.32-38 (in Chinese).

[7] Lasley, S.M., Green, M.C., Gilbert, M.E., 2001. Rat hippocampal NMDA receptor binding as a function of chronic lead exposure level. Neurotoxicol Teratol, 23(2):185-189.

[8] Monyer, H., Sprengel, R., Shoepfer, R., 1992. Heteromeric NMDA receptors: Molecular and functional distinction of subtypes. Science, 256:1217-1221.

[9] O’Dell, T.J., Hawkins, R.D., Kandel, E.R., 1991. Tests of the roles of two diffusible substances in long-term potentiation: Evidence for nitric oxide as a possible early retrograde messenger. Proc Natl Acad Sci USA, 88(24):11285-11289.

[10] Zhang, X.Y., Lin, A.P., Ruan, D.Y., Liu, J., 2002. Effect of developmental lead exposure on the expression of specific NMDA receptor subunit mRNAs in the hippocampus of neonatal rats by digoxigenin-labeled in situ hybridization histochemistry. Neurotoxicol Teratol, 24(2):149-160.

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