Zhang Xiao-yan, Liu Ai-Ping, Ruan Di-Yun, Liu Jin
School of Life Science, University of Science and Technology of China, Hefei, Anhui, China.
Neurotoxicol Teratol. 2002 Mar-Apr;24(2):149-60. doi: 10.1016/s0892-0362(01)00210-0.
The N-methyl-D-aspartate (NMDA) receptor has an important role in learning and memory. In this study, the effects of chronic Pb exposure on NMDA receptor subunit mRNAs expression in the developing rat hippocampus were examined by digoxigenin (DIG)-labeled in situ hybridization. In Pb-exposed rats, hippocampal NR1-2a mRNA levels were significantly increased in CA1, CA4 and DG subfields at 15 days of age and CA4 and DG subfields at 20 days of age. The lead (Pb) exposure resulted in a significant increase of NR2D mRNA levels in CA1, CA2, CA4 and DG hippocampal subfields at 20 days of age. Hippocampal NR2A mRNA levels were significantly decreased in CA1, CA2, CA3 and DG subfields from 15-day-old Pb-exposed rats and CA1, CA3 and DG subfields from 20-day-old Pb-exposed rats. Hippocampal NR3A mRNA levels were also significantly decreased in CA1, CA4 and DG subfields at 15 days of age and CA1 and DG subfields at 20 days of age in Pb-exposed rats. The Pb-induced subunit specific changes in hippocampal NMDA receptor subunit mRNA expression may lead to abnormality of natural NMDA stoichiometry and interfere with the physiological function of the NMDA receptor in the development of defined neuronal connections.
N-甲基-D-天冬氨酸(NMDA)受体在学习和记忆中起着重要作用。在本研究中,采用地高辛(DIG)标记的原位杂交技术,检测了慢性铅暴露对发育中大鼠海马体NMDA受体亚基mRNA表达的影响。在铅暴露大鼠中,15日龄时CA1、CA4和齿状回(DG)亚区以及20日龄时CA4和DG亚区的海马NR1-2a mRNA水平显著升高。铅暴露导致20日龄时CA1、CA2、CA4和DG海马亚区的NR2D mRNA水平显著增加。15日龄铅暴露大鼠的CA1、CA2、CA3和DG亚区以及20日龄铅暴露大鼠的CA1、CA3和DG亚区的海马NR2A mRNA水平显著降低。15日龄时CA1、CA4和DG亚区以及20日龄时CA1和DG亚区的海马NR3A mRNA水平在铅暴露大鼠中也显著降低。铅诱导的海马NMDA受体亚基mRNA表达的亚基特异性变化可能导致天然NMDA化学计量异常,并在特定神经元连接发育过程中干扰NMDA受体的生理功能。