Gottesfeld Z, Garcia C J, Lingham R B, Chronister R B
Department of Neurobiology and Anatomy, University of Texas Medical School, Houston 77025.
Neuroscience. 1989;29(3):715-23. doi: 10.1016/0306-4522(89)90143-7.
This study examined the consequences of alcohol (ethanol) exposure during fetal life on lesion-induced dopaminergic synapse responsiveness (plasticity) in the olfactory tubercle of the adult rat. Normally, in the olfactory tubercle, olfactory bulbectomy elicits alterations in pre- and postsynaptic dopaminergic markers, including, respectively, (1) increased tyrosine hydroxylase activity and immunoreactivity, which is associated with dopaminergic axon sprouting, and (2) increased dopaminergic receptor density and potentiated dopamine activation of adenylate cyclase. We have utilized biochemical and quantitative immunocytochemical methodology to examine these synaptic markers in olfactory bulbectomized or sham-operated adult rats. These animals were offspring of dams which were administered one of the following diets during pregnancy: (1) liquid diet containing 35% ethanol-derived calories ad libitum; (2) liquid diet containing an isocaloric amount of maltose-dextrin instead of ethanol, pair-fed; or (3) unaltered liquid diet ad libitum. The results show that prenatal alcohol exposure leads to suppression of the lesion-elicited dopaminergic synapse responsiveness in the olfactory tubercle. There were no significant differences between offspring born to control and pair-fed animals, indicating that the observed abnormalities were not due to alterations in their nutritional status. In conclusion, the present data are a biochemical and quantitative immunocytochemical demonstration of impaired lesion-induced synaptic responsiveness. This renders a new dimension in support of previous evidence indicating that prenatal alcohol exposure leads to altered neuroanatomical, neuroendocrinological and behavioral responsiveness to various challenges. Such impaired synaptic responsiveness may underlie brain functional abnormalities characteristic of fetal alcohol syndrome.
本研究检测了成年大鼠胎儿期酒精(乙醇)暴露对损伤诱导的嗅结节多巴胺能突触反应性(可塑性)的影响。正常情况下,在嗅结节中,切除嗅球会引起突触前和突触后多巴胺能标志物的改变,分别包括:(1)酪氨酸羟化酶活性和免疫反应性增加,这与多巴胺能轴突发芽有关;(2)多巴胺能受体密度增加以及多巴胺对腺苷酸环化酶的激活增强。我们利用生化和定量免疫细胞化学方法检测了成年大鼠嗅球切除或假手术后这些突触标志物的变化。这些动物是孕期接受以下饮食之一的母鼠的后代:(1)随意摄入含35%乙醇热量的液体饮食;(2)摄入等热量麦芽糖糊精而非乙醇的液体饮食,配对喂养;或(3)随意摄入未改变的液体饮食。结果显示,产前酒精暴露会抑制损伤诱导的嗅结节多巴胺能突触反应性。对照组和配对喂养组动物所产后代之间无显著差异,这表明观察到的异常并非由其营养状况改变所致。总之,本研究数据通过生化和定量免疫细胞化学方法证明了损伤诱导的突触反应性受损。这为先前的证据提供了新的支持,表明产前酒精暴露会导致对各种刺激的神经解剖学、神经内分泌学和行为反应性改变。这种受损的突触反应性可能是胎儿酒精综合征特征性脑功能异常的基础。