Heaton M B, Swanson D J, Paiva M, Walker D W
Department of Neuroscience, University of Florida Brain Institute, Gainesville 32610-0244, USA.
J Comp Neurol. 1996 Jan 1;364(1):113-20. doi: 10.1002/(SICI)1096-9861(19960101)364:1<113::AID-CNE10>3.0.CO;2-#.
This study investigated the influence of ethanol exposure throughout gestation on cholinergic development within the rat striatal region. Pregnant Long-Evans rats were maintained on three diets throughout gestation: A liquid diet in which ethanol accounted for 35-39% of the total calories, a similar diet with the isocaloric substitution of sucrose for ethanol, and a lab chow control diet. At postnatal days 14 and 60 (P14 and P60), the striatal regions of the offspring were analyzed for the number of cholinergic neurons, via choline acetyltransferase (ChAT) immunostaining. The area of the striatum was also measured in these animals. At P14, P21, and P60, ChAT activity was assessed in the same region. These analyses revealed a significant increase in the number of cholinergic striatal neurons at P14 in the animals which had been exposed prenatally to ethanol. This increase was transient, however, with equal numbers of ChAT-positive cells found in all three groups by adulthood (P60). The brain weights of the ethanol-exposed animals were significantly reduced at P14 and P21, but were comparable to controls by P60. There were no significant differences in the striatal area or the overall volume of the region assessed, however, at either P14 or P60. Although there were some increases in ChAT activity across the ages viewed (most notably between P14 and P21), there were no effects of diet on ChAT activity at any age assessed. It is proposed that the increased numbers of cholinergic neurons could be a function of errors in migration, enhanced neurogenesis, diminished cell death, alterations in gene expression, or increased cell survival as a result of alterations in neurotrophic factor production or availability.
本研究调查了孕期全程暴露于乙醇对大鼠纹状体区域胆碱能发育的影响。怀孕的Long-Evans大鼠在整个孕期维持三种饮食：一种液体饮食，其中乙醇占总热量的35 - 39%；一种类似的饮食，用等热量的蔗糖替代乙醇；以及一种实验室常规饲料对照饮食。在出生后第14天和60天（P14和P60），通过胆碱乙酰转移酶（ChAT）免疫染色分析后代的纹状体区域胆碱能神经元数量。还测量了这些动物的纹状体面积。在P14、P21和P60时，评估同一区域的ChAT活性。这些分析显示，产前暴露于乙醇的动物在P14时，纹状体胆碱能神经元数量显著增加。然而，这种增加是短暂的，到成年期（P60）时，三组中ChAT阳性细胞数量相等。乙醇暴露动物的脑重量在P14和P21时显著降低，但到P60时与对照组相当。然而，在P14或P60时，所评估区域的纹状体面积或总体积没有显著差异。尽管在所观察的各个年龄段ChAT活性都有一些增加（最显著的是在P14和P21之间），但在任何评估的年龄，饮食对ChAT活性都没有影响。有人提出，胆碱能神经元数量的增加可能是由于迁移错误、神经发生增强、细胞死亡减少、基因表达改变，或者是由于神经营养因子产生或可用性改变导致细胞存活增加。
