NMDAR-2A subunit protein expression is reduced in the hippocampus of rats exposed to Pb2+ during development
NMDAR-2A subunit protein expression is reduced in the hippocampus of rats exposed to Pb2+ during development
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DOI：
10.1016/s0169-328x(99)00005-4
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发表时间：
1999-03-20
期刊：
影响因子：
--
通讯作者：
Guilarte, TR
中科院分区：
文献类型：
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作者：
Nihei, MK;Guilarte, TR
铅（Pb 2+）的慢性暴露会导致儿童的学习和记忆缺陷以及发育中大鼠的空间学习缺陷。N-甲基-D-天冬氨酸受体（NMDAR）已被确定为Pb 2+诱导的神经毒性的主要靶点。在发育过程中长期暴露于Pb 2+的大鼠的大脑中观察到NMDAR亚基基因表达的依赖性变化[T.R. Guilarte，J.L. McGlothan，Hippocampus NMDA receptor mRNA exceeds subunit specific changes during developmental lead exposure，Brain Res. 790（1998）98-107]。这些变化出现在血铅2+水平范围为20-60微克/分升。在本研究中使用同窝仔以确定基因表达的变化是否反映在蛋白质水平中。通过Western印迹和光密度分析，测定了出生后第7、14、21和28天大鼠海马和皮质中NR 1、NR 2A和NR 2B亚基蛋白水平。海马中NR 2A亚基蛋白表达的治疗效果是明显的（F-1.28 = 10.224，p < 0.01）。在PND 14、21和28铅暴露大鼠中，NR 2A亚基蛋白分别比对照水平降低了40%、19%和27%。平均值比较表明，PND 14的大鼠表现出最显著的NR 2A降低（p < 0.001）。这些数据与我们以前的发现减少NR 2A mRNA发现在海马锥体细胞和颗粒细胞的铅暴露大鼠。铅暴露在发展过程中没有影响NR 1或NR 2B亚基蛋白在海马在任何年龄的表达。在任何年龄的皮质中的任何亚基上均未观察到影响。海马中NMDAR-2A亚基蛋白的发育概况通过慢性暴露于Pb 2+而特异性改变。这些数据表明，组成的亚基NMDAR可能会改变铅暴露大鼠。(C)1999 Elsevier Science B. V.保留所有权利。
Chronic exposure to lead (Pb2+) produces deficits of learning and memory in children and spatial learning deficits in developing rats. The N-methyl-D-aspartate receptor (NMDAR) has been identified as a principal target for Pb2+-induced neurotoxicity. Age-dependent changes in NMDAR subunit gene expression were observed in hippocampi of rats chronically exposed to Pb2+ during development [T.R. Guilarte, J.L. McGlothan, Hippocampal NMDA receptor mRNA undergoes subunit specific changes during developmental lead exposure, Brain Res. 790 (1998) 98-107]. These changes were present at blood Pb2+ levels ranging from 20-60 mu g/dl. Littermates were used in the present study to determine whether the changes in gene expression were reflected in protein levels. NR1, NR2A, and NR2B subunit protein levels were measured in rat hippocampus and cortex at post-natal days (PND) 7, 14, 21, and 28 by Western blot and densitometric analysis. A treatment effect was apparent for NR2A subunit protein expression in the hippocampus (F-1.28 = 10.224, p < 0.01). NR2A subunit protein was reduced by 40%, 19%, and 27% from control levels in PND14, 21, and 28 Pb2+-exposed rats, respectively. Mean comparisons indicated that rats at PND14 exhibited the most significant reduction of NR2A (p < 0.001). These data concur with our previous finding of reduced NR2A mRNA found in hippocampal pyramidal and granule cells of Pb2+-exposed rats. Pb2+ exposure during development had no effect on NR1 or NR2B subunit protein expression in the hippocampus at any age. No effect was observed on any subunit in the cortex at any age. The developmental profile of the NMDAR-2A subunit protein in the hippocampus is specifically changed by chronic exposure to Pb2+. These data suggest that composition of subunits comprising NMDAR may be altered in Pb2+-exposed rats. (C) 1999 Elsevier Science B.V. All rights reserved.