Schambra U B, Lauder J M, Petrusz P, Sulik K K
Department of Cell Biology and Anatomy, School of Medicine, University of North Carolina, Chapel Hill 27599-7090.
Int J Dev Neurosci. 1990;8(5):507-22. doi: 10.1016/0736-5748(90)90043-2.
Acute maternal ethanol administration to C57B1/6J mice on gestational day 7 (GD7) results in facial and brain abnormalities similar to those reported in human fetal alcohol syndrome (FAS). Using this model, we assessed the damage to brain structures using histological methods and changes in developing neurotransmitter systems with immunocytochemistry. Cholinergic neurons in the forebrain were stained with a monoclonal antibody to choline acetyltransferase (ChAT). Catecholaminergic neurons in the midbrain and serotoninergic neurons in the hindbrain were stained with polyclonal antisera to tyrosine hydroxylase (TH) and serotonin (5-HT), respectively. Forebrain deficiencies, including loss of midline structures (olfactory bulbs, midline septation, medial septal area) and deficits in lateral and dorsal regions (neostriatum and cerebral cortex) were found in both GD14 embryos and GD18 fetuses. In severely affected offspring, complete loss of the septal region resulted in conjoined lateral ventricles and a reduction in the thickness of the ventricular zone surrounding the single ventricle, as well as a severe loss of ChAT neurons which would normally be located in this territory. However, no consistent changes were seen in the distribution or size of TH or 5-HT neuronal cell groups in the midbrain and hindbrain. These differences in effects on specific neurotransmitter systems reflect the fact that the forebrain is most severely affected by early ethanol administration, whereas the hindbrain is relatively spared. Such differential effects could produce an imbalance in developing neurotransmitter systems in the embryonic and fetal brain, which could explain some of the functional deficits observed in children with FAS.
在妊娠第7天（GD7）给C57B1/6J小鼠急性给予乙醇，会导致其面部和大脑出现异常，类似于人类胎儿酒精综合征（FAS）所报告的情况。利用该模型，我们采用组织学方法评估了对脑结构的损伤，并通过免疫细胞化学方法评估了发育中的神经递质系统的变化。前脑胆碱能神经元用抗胆碱乙酰转移酶（ChAT）单克隆抗体染色。中脑的儿茶酚胺能神经元和后脑的5-羟色胺能神经元分别用抗酪氨酸羟化酶（TH）和5-羟色胺（5-HT）多克隆抗血清染色。在GD14胚胎和GD18胎儿中均发现前脑缺陷，包括中线结构（嗅球、中线分隔、内侧隔区）缺失以及外侧和背侧区域（新纹状体和大脑皮层）的缺陷。在受严重影响的后代中，隔区完全缺失导致侧脑室相连，围绕单个脑室的脑室带厚度减小，以及通常位于该区域的ChAT神经元严重缺失。然而，中脑和后脑的TH或5-HT神经元细胞群的分布或大小未见一致变化。对特定神经递质系统的这些影响差异反映了这样一个事实，即前脑受早期乙醇给药的影响最为严重，而后脑相对未受影响。这种差异效应可能会在胚胎和胎儿大脑发育中的神经递质系统中产生失衡，这可以解释FAS患儿中观察到的一些功能缺陷。
