Hughes P D, Kim Y N, Randall P K, Leslie S W
Division of Pharmacology and Toxicology, College of Pharmacy and Institute for Neuroscience, The University of Texas at Austin, 78712-1074, USA.
Alcohol Clin Exp Res. 1998 Sep;22(6):1255-61.
The effects of prenatal ethanol exposure on the NMDAR1 protein expression (postnatal days 1 and 7) and on the developmental profile of the NMDAR2A and NMDAR2B subunits in rat forebrain and hippocampus were investigated. Forebrain and hippocampal membrane proteins were isolated from pups of various ages (postnatal days 1 to 21) from prenatally ethanol exposed, pair-fed and ad libitum control groups. A semiquantitative immunoblot procedure was used with antibodies raised against the NMDAR1, NMDAR2A, and the NMDAR2B subunits to assess the NMDA subunit protein expression in the samples. NMDAR1 protein expression was unaffected by prenatal ethanol exposure at postnatal day 1 or 7 in both the forebrain and hippocampus. NMDAR2A protein expression levels rose rapidly in both forebrain and hippocampus during the time frame of study. Prenatal ethanol exposure caused a significant reduction in protein expression levels of the NMDAR2A in forebrain through postnatal day 14. NMDAR2B protein expression levels were high throughout the study in both forebrain and hippocampus. Prenatal ethanol exposure significantly reduced protein expression of the NMDAR2B in the forebrain (through postnatal day 14) and hippocampus (up to day 7). The results suggest that there may be a link between the depressed expression of the NMDAR2 subunits and the neurodevelopmental disorders associated with fetal ethanol exposure.
研究了产前乙醇暴露对大鼠前脑和海马中NMDAR1蛋白表达(出生后第1天和第7天)以及NMDAR2A和NMDAR2B亚基发育情况的影响。从产前乙醇暴露组、配对喂养组和自由摄食对照组的不同年龄(出生后第1天至21天)幼崽中分离前脑和海马膜蛋白。使用针对NMDAR1、NMDAR2A和NMDAR2B亚基的抗体进行半定量免疫印迹实验,以评估样品中NMDA亚基蛋白的表达。出生后第1天和第7天,前脑和海马中的NMDAR1蛋白表达不受产前乙醇暴露的影响。在研究期间,前脑和海马中的NMDAR2A蛋白表达水平迅速上升。产前乙醇暴露导致前脑中NMDAR2A蛋白表达水平在出生后第14天之前显著降低。在整个研究过程中,前脑和海马中的NMDAR2B蛋白表达水平都很高。产前乙醇暴露显著降低了前脑(出生后第14天之前)和海马(直至第7天)中NMDAR2B的蛋白表达。结果表明,NMDAR2亚基表达降低与胎儿乙醇暴露相关的神经发育障碍之间可能存在联系。