ALCOHOL-INDUCED NEURONAL LOSS IN DEVELOPING RATS - INCREASED BRAIN-DAMAGE WITH BINGE EXPOSURE
ALCOHOL-INDUCED NEURONAL LOSS IN DEVELOPING RATS - INCREASED BRAIN-DAMAGE WITH BINGE EXPOSURE
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DOI：
10.1111/j.1530-0277.1990.tb00455.x
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发表时间：
1990-02-01
期刊：
影响因子：
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通讯作者：
WEST, JR
中科院分区：
文献类型：
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作者：
BONTHIUS, DJ;WEST, JR
使用妊娠晚期胎儿酒精暴露的大鼠模型来确定是否较小的每日剂量的酒精可以诱导更严重的微脑畸形和神经元损失比较大的剂量，如果小剂量的消耗以这样一种方式，它产生更高的血液酒精浓度（BAC）。还研究了发育中的脑内区域差异对酒精诱导的神经元损失的可能性。Sprague-Dawley大鼠幼仔在出生后第4-10天（与人类妊娠晚期相似的大脑快速生长期）人工饲养。两组接受4.5 g/kg的每日酒精剂量，在12次每日喂食中的4次中以5.1%溶液给药，或在12次喂食中的2次中以10.2%溶液给药。第三组在每次喂食中接受更高的日剂量（6.6 g/kg），作为2.5%溶液给药。还饲养了胃造口术和胃排空对照动物。在出生后第10天，对动物进行灌注，并获得脑重量。在海马结构中，对CA 1和CA 2/3区的锥体细胞，CA 4区的多种细胞类型和齿状回的颗粒细胞进行了细胞计数。在小脑中，在小脑蚓部的10个小叶中的每一个中计数浦肯野细胞和颗粒细胞。与对照组相比，浓缩为两次或四次喂食的较低日剂量（4.5 g/kg）产生了较高的最大BAC（平均值分别为361.6和190.7 mg/dl）和显著的小脑畸形和细胞丢失。连续给予较高的日剂量（6.6 g/kg），导致BAC较低（平均值为39.2 mg/dl），未诱导微脑畸形或细胞丢失。神经元对酒精的脆弱性存在明显的区域差异。在海马，CA 1神经元数量显着减少，只有最浓缩的酒精治疗，而CA 3，CA 4，和齿状回人口没有减少与任何酒精治疗。在小脑，一些小叶遭受显着更大的浦肯野细胞和颗粒细胞的损失比别人。在酒精暴露时浦肯野细胞最成熟的区域最容易受到浦肯野细胞损失的影响。
A rat model of third trimester fetal alcohol exposure was used to determine whether a smaller daily dose of alcohol can induce more severe microencephaly and neuronal loss than a larger dose, if the small dose is consumed in such a way that it produces higher blood alcohol concentrations (BACs). The possibility of regional differences within the developing brain to alcohol-induced neuronal loss was also investigated. Sprague-Dawley rat pups were reared artificially over postnatal Days 4-10 (a period of rapid brain growth similar to that of the human third trimester). Two groups received a daily alcohol dose of 4.5 g/kg, adminstered either as a 5.1% solution in four of the 12 daily feedings or as a 10.2% solution in two of the 12 feedings. A third group received a higher daily dose (6.6 g/kg) administered as a 2.5% solution in every feeding. Gastrostomy and suckle controls were also reared. On postnatal Day 10, the animals were perfused, and brain weights and obtained. In the hippocampal formation, cell counts were made of the pyramidal cells of fields CA1 and CA2/3, the multiple cell types of CA4 and the granule cells of the dentate gyrus. In the cerebellum, Purkinje cells and granule cells were counted in each of the ten lobules of the vermis. The lower daily dose (4.5 g/kg) condensed into two or four feedings produced high maximum BACs (means of 361.6 and 190.7 mg/dl, respectively) and significant microencephaly and cell loss, relative to controls. The higher daily dose (6.6 g/kg), administered continuously, resutled in low BACs (mean of 39.2 mg/dl) and induced no microencephaly or cell loss. Regional differences in neuronal vulnerability to alcohol were evident. In the hippocampus, CA1 neuronal number was significantly reduced only by the most condensed alcohol treatment, while CA3, CA4, and dentate gyrus populations were not reduced with any alcohol treatment. In the cerebellum, some lobules suffered significantly greater Purkinje cell loss and granule cell loss than did others. The regions in which Purkinje cells were most mature at the time of the alcohol exposure were the most vulnerable to Purkinje cell loss.