Wang Xin-Mei, Liu Wen-Jun, Zhang Rong, Zhou Yi-Kai
MOE Key Laboratory of Environment and Health, Institute of Environmental Medicine, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China.
Toxicol Ind Health. 2013 Sep;29(8):686-96. doi: 10.1177/0748233712436641. Epub 2012 Feb 23.
The effect of different periods of lead exposure on deficits of learning and memory is still unclear. In this study, we conduct in vivo experiment to investigate the critical stages when lead induced neurotoxicity in rats and its underlying mechanisms in some critical stages. Rats were exposed to 0.2% mg/ml lead acetate solution via drinking water during gestation, lactation and ablactation periods. Behavior deficits were found in gestation and lactation. N-Methyl-d-aspartate (NMDA) receptor subunit 2A (NR2A) increased during gestation both in hippocampus and cerebral cortex compared to the control group; in all treatment groups NR2B decreased in hippocampus and in cerebral cortex during the lactation period. Meanwhile, in hippocampus metabotropic glutamate receptor 1 (mGluR1) decreased during gestation and lactation periods but increased during the ablactation period. These observations suggest that exposure to lead in gestation and lactation periods could cause neurobehavioral deficits which extend to adulthood, and lactation was a more sensitive period for lead exposure. Furthermore, the abnormal expression of NMDA receptor 2 (NMDAR 2) subunits and mGluR1 are likely to be associated with the impairment.
不同时期铅暴露对学习和记忆缺陷的影响仍不清楚。在本研究中,我们进行体内实验,以探究铅诱导大鼠神经毒性的关键阶段及其在某些关键阶段的潜在机制。在妊娠、哺乳和断奶期间,通过饮用水让大鼠接触0.2%毫克/毫升的醋酸铅溶液。在妊娠和哺乳期发现行为缺陷。与对照组相比,妊娠期间海马体和大脑皮层中的N-甲基-D-天冬氨酸(NMDA)受体亚基2A(NR2A)增加;在所有治疗组中,哺乳期海马体和大脑皮层中的NR2B减少。同时,在海马体中,代谢型谷氨酸受体1(mGluR1)在妊娠和哺乳期减少,但在断奶期增加。这些观察结果表明,妊娠和哺乳期接触铅可导致神经行为缺陷并延续至成年期,哺乳期是铅暴露更敏感的时期。此外,NMDA受体2(NMDAR 2)亚基和mGluR1的异常表达可能与损伤有关。