Nagahara A H, Handa R J
Department of Cell Biology, Neurobiology and Anatomy, Loyola University Chicago, Stritch School of Medicine, Maywood, IL 60153, USA.
Alcohol Clin Exp Res. 1995 Dec;19(6):1389-97. doi: 10.1111/j.1530-0277.1995.tb00997.x.
The present study examined fetal alcohol effects (FAE) on the induction of the immediate early genes (IEGs) c-fos, jun B, c-jun, and zif268 mRNAs in the prefrontal cortex, hippocampus, and other brain regions after testing in an alternation task. Subjects were female offspring of Sprague-Dawley rats fed either a 35% ethanol-derived calorie diet, pair-fed with sucrose, or control-fed with laboratory chow during the last week of gestation. At 75-85 days of age, rats were food-deprived and trained in a t-maze for food reward. Then rats were tested at 5-sec, 30-sec, or 60-sec delays on each of 6 days. On the day of killing, a subset of rats was tested at the 60-sec delay for 12 trials and killed 30 min after testing. The remaining animals were killed from their home cage and acted as controls. Expression of the four IEG mRNAs was examined in the brains of these animals using in situ hybridization. FAE rats showed a memory deficit at the 60-sec delay (p < 0.05), but not at the 0-sec or 30-sec delays. Testing in the alternation task induced a significant elevation of c-fos, c-jun, jun B, and zif268 mRNA expression in the prefrontal cortex, hippocampal subfields CA1 and CA3, and several cortical areas. However, FAE rats showed a significantly smaller elevation of both c-fos and jun B mRNA levels in the orbital, prelimbic, and anterior cingulate regions of the prefrontal cortex (p < 0.05). FAE animals also showed a lower expression of jun B mRNA in the caudate nucleus. Significant correlations between the mean performance at the 60-sec delay and mRNA expression of c-fos, jun B, and zif268 in the prefrontal cortical regions (p < 0.05) were observed. These findings suggest that fetal alcohol exposure produces changes in the adult prefrontal cortex that may contribute to the behavioral deficit in the alternation task.
本研究检测了胎儿酒精效应（FAE）对前额叶皮质、海马体及其他脑区中即刻早期基因（IEG）c-fos、jun B、c-jun和zif268 mRNA诱导的影响，实验采用交替任务测试。实验对象为斯普拉格-道利大鼠的雌性后代，在妊娠最后一周，它们分别被喂食含35%乙醇热量的饮食、与蔗糖配对喂食或用实验室标准食物正常喂食。在75 - 85日龄时，大鼠禁食，并在T型迷宫中接受食物奖励训练。然后在6天中的每一天，对大鼠进行5秒、30秒或60秒延迟测试。在处死当天，一部分大鼠接受60秒延迟测试12次，并在测试后30分钟处死。其余动物从其饲养笼中取出处死，作为对照。使用原位杂交技术检测这些动物大脑中四种IEG mRNA的表达。FAE大鼠在60秒延迟时表现出记忆缺陷（p < 0.05），但在0秒或30秒延迟时没有。交替任务测试使前额叶皮质、海马亚区CA1和CA3以及几个皮质区域的c-fos、c-jun、jun B和zif268 mRNA表达显著升高。然而，FAE大鼠在前额叶皮质的眶部、前边缘和前扣带回区域中，c-fos和jun B mRNA水平的升高明显较小（p < 0.05）。FAE动物在尾状核中jun B mRNA的表达也较低。观察到在60秒延迟时的平均表现与前额叶皮质区域中c-fos、jun B和zif268的mRNA表达之间存在显著相关性（p < 0.05）。这些发现表明，胎儿酒精暴露会导致成年前额叶皮质发生变化，这可能是交替任务中行为缺陷的原因。
