Nixon Kimberly, Hughes Peter D, Amsel Abram, Leslie Steven W
Department of Psychology, Waggoner Center for Alcohol and Addiciton Research, University of Texas, Austin, Texas, USA.
Alcohol Clin Exp Res. 2004 Jan;28(1):105-12. doi: 10.1097/01.ALC.0000106311.88523.7B.
The N-methyl-D-aspartate receptor (NMDAR), a subtype of glutamate receptor, is essential for normal neurodevelopment. The brain growth spurt, which is both prenatal and postnatal in the rat, is a time when the brain is especially sensitive to the effects of a teratogen, such as alcohol. Changes in NMDAR function after early perinatal exposure to ethanol (EtOH) may be related to alterations in the expression of secondary subunits. Thus, we investigated the expression of the NR1, NR2A, and NR2B subunits after combined prenatal and postnatal exposure to EtOH.
A binge model was used to administer EtOH (5 g/kg) or isocaloric vehicle to pregnant female rats followed by EtOH (6.2 g/kg) or isocaloric control diet from postnatal days 4 through 9 via an artificial rearing method. Proteins from crude membrane homogenates isolated from cortex and hippocampus at postnatal day 10, 14, or 21 were separated in a standard Western blot procedure.
The expression of the NR2A subunit of EtOH-exposed pups showed a significant increase at postnatal day 10 in hippocampus compared with diet controls. No significant changes were seen for any other subunit in either region.
The up-regulation of NR2A during EtOH withdrawal is consistent with compensatory changes to prolonged inhibition of the NMDAR. These results indicate that postnatal exposure to ethanol produces distinct effects on the NMDAR, which may underlie deficits associated with alcohol-related neurodevelopmental disorder.
N-甲基-D-天冬氨酸受体（NMDAR）是谷氨酸受体的一种亚型，对正常神经发育至关重要。大鼠在产前和产后都会经历脑发育快速期，在此期间大脑对致畸剂（如酒精）的影响尤为敏感。围产期早期暴露于乙醇（EtOH）后NMDAR功能的变化可能与辅助亚基表达的改变有关。因此，我们研究了产前和产后联合暴露于EtOH后NR1、NR2A和NR2B亚基的表达情况。
采用暴饮暴食模型，给怀孕的雌性大鼠灌胃EtOH（5 g/kg）或等热量载体，然后从出生后第4天到第9天，通过人工饲养方法给幼鼠灌胃EtOH（6.2 g/kg）或等热量对照饮食。在出生后第10、14或21天，从皮质和海马体分离出粗制膜匀浆中的蛋白质，采用标准蛋白质印迹法进行分离。
与饮食对照组相比，暴露于EtOH的幼鼠海马体中NR2A亚基在出生后第10天的表达显著增加。在这两个区域中，其他亚基均未观察到显著变化。
EtOH戒断期间NR2A的上调与NMDAR长期受抑制后的代偿性变化一致。这些结果表明，产后暴露于乙醇对NMDAR产生了明显影响，这可能是与酒精相关神经发育障碍相关缺陷的基础。
