Alcohol-induced Purkinje cell loss with a single binge exposure in neonatal rats: A stereological study of temporal windows of vulnerability
Alcohol-induced Purkinje cell loss with a single binge exposure in neonatal rats: A stereological study of temporal windows of vulnerability
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DOI：
10.1097/00000374-199706000-00028
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发表时间：
1997-06-01
影响因子：
3.2
通讯作者：
Eilers, AT
中科院分区：
文献类型：
--
作者：
Goodlett, CR;Eilers, AT
先前的研究表明，新生早期大鼠对酗酒相关的小脑浦肯野细胞丢失的易感性增加，出生后第一周是一个显著的敏感期。在这项研究中，使用体视学光学分割仪，在最脆弱的新生儿时期[出生后第4天]或较晚的较不脆弱时期(PD 9)，对给予单一铰链状酒精暴露的各组大鼠的浦肯野细胞总数进行了无偏计数。采用人工饲养的方法，在指定日期连续两次喂养大鼠，分别在PD 4和PD 9罐头给予6.6g/kg酒精，以15%(v/v)的奶粉溶液递送。中心组包括人工饲养的胃造口术对照组和正常饲养的哺乳对照组。Pd4组和Pb9组的平均峰值血酒精浓度无差异，分别为374和347 mg/dl。大鼠在PD 27时进行灌流。从连续的小脑冰冻切片中随机取一份均匀的切片，硫代宁染色，用三维光学分割仪从每一张切片上的位置的均匀随机样本中计数浦肯野细胞。乳汁对照组和胃造瘘组的浦肯野细胞数无差异，平均分别为3.94(+/-0.19)和3.58(+/-0.22)×10(5)细胞。过度暴露于PD-4可引起明显的细胞丢失(平均2.05+/-0.20×10(5)个浦肯野细胞)，而过度暴露PD-9不能诱导显著的浦肯野细胞(3.70+/-0.39×10(5)个浦肯野细胞)。这些发现证实了单次新生儿酗酒暴露会导致病理性浦肯野细胞丢失，前提是它发生在易损性增强的时期，与树突状突起生长的早期阶段重合。
Previous research has shown that the early neonatal period of rats is one of enhanced vulnerability to cerebellar Purkinje cell loss associated with binge-like alcohol exposure, with a prominent sensitive period during the first neonatal week. In this study, an unbiased count of the total number of Purkinje cells was obtained using the stereological optical fractionator, in groups of rats given a single hinge-like alcohol exposure either during the most vulnerable neonatal period [postnatal day (PD) 4] or during a later, less vulnerable period (PD 9). Using artificial rearing methods, rats were given 6.6 g/kg of alcohol either on PD 4 or can PD 9, delivered as a 15% (v/v) solution in milk formula on two consecutive feedings of the designated day. Central groups included an artificially reared gastrostomy control and a normally reared suckle control. The mean peak blood alcohol concentrations were no: different between the PD 4 and PB 9 alcohol groups, averaging 374 and 347 mg/dl, respectively. The rats were perfused on PD 27. A uniform random sample of sections was obtained from serial frozen sections through the cerebellum, stained with thionin, and Purkinje cells were counted from a uniform random sample of locations on each section with the three-dimensional optical fractionator. The number of Purkinje cells in the suckle control and gastrostomy control groups did not differ from each other, averaging 3.94 (+/-0.19) and 3.58 (+/-0.22) x 10(5) cells, respectively. Binge exposure on PD 4 induced significant cell loss (mean of 2.05 +/- 0.20 x 10(5) Purkinje cells), whereas binge exposure an PD 9 did not induce significant Purkinje cell lass (3.70 +/- 0.39 x 10(5) Purkinje cells). These findings confirm that a single neonatal binge alcohol exposure produces pathological Purkinje cell loss, provided that it occurs during the period of enhanced vulnerability coinciding with the early stages of dendritic outgrowth.