Interaction of thiamine deficiency and voluntary alcohol consumption disrupts rat corpus callosum ultrastructure
Interaction of thiamine deficiency and voluntary alcohol consumption disrupts rat corpus callosum ultrastructure
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DOI：
10.1038/sj.npp.1301332
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发表时间：
2007-10-01
影响因子：
7.6
通讯作者：
Pfefferbaum, Adolf
中科院分区：
文献类型：
--
作者：
He, Xiaohua;Sullivan, Edith V.;Pfefferbaum, Adolf
酒精和硫胺素缺乏在引起脑损伤中的相对作用在没有Wernicke - Korsakoff综合征的酗酒者中仍然存在争议。对饮酒和饮食的实验控制在人类中是不可能的，但可以在动物模型中完成。本实验旨在区分硫胺素缺乏和自愿饮酒对胼胝体宏观和超微结构的单独和联合影响。成年雄性嗜酒(P)大鼠（9只长期酒精暴露组和9只水对照组）接受2周的硫胺素缺乏饮食。有四组：先前暴露于酒精的五只大鼠用硫胺素（一种硫胺素磷酸化抑制剂）治疗；5只从未接触过酒精的大鼠用硫胺素治疗；4只酒精暴露大鼠用硫胺素治疗；4只从未接触过酒精的老鼠用硫胺素治疗。第14天，所有18只大鼠的硫胺素恢复；2周后，10只经硫胺素治疗的大鼠腹腔注射硫胺素。大鼠在598日龄时给予硫胺素治疗61天后灌注。解剖大脑，计算重量和体积。矢状面切片染色以测量白质结构。用透射电镜检查胼胝体，测定髓鞘纤维密度、纤维直径和髓鞘厚度。与酒精/硫胺素和水/硫胺素组相比，酒精/硫胺素组胼胝体明显变薄，纤维密度更高，小纤维百分比更高，髓鞘变薄。几项测量显示出分级效应，其中酒精/硫胺素组比水/硫胺素组有更大的病理，而水/硫胺素组比两个硫胺素充满的组有更大的病理。在所有16只大鼠中，更薄的髓鞘与更高比例的小纤维相关。髓鞘厚度和轴突直径共同占小纤维百分比相关方差的71%。酒精/硫胺素组的显著异常和酒精暴露/硫胺素充满组的无异常表明硫胺素缺乏导致白质损伤。在双重或单一治疗的动物中，分级异常支持酒精暴露和硫胺素消耗的复合效应，并表明在人类酒精相关脑损伤中，酒精和硫胺素缺乏之间可能存在相互作用。
The relative roles of alcohol and thiamine deficiency in causing brain damage remain controversial in alcoholics without the Wernicke Korsakoff syndrome. Experimental control over alcohol consumption and diet are impossible in humans but can be accomplished in animal models. This experiment was designed to differentiate the separate and combined effects on the macro-and ultrastructure of the corpus callosum of thiamine deficiency and voluntary alcohol consumption. Adult male alcohol-preferring (P) rats (9 chronically alcohol-exposed and 9 water controls) received a thiamine-deficient diet for 2 weeks. There were four groups: five rats previously exposed to alcohol were treated with pyrithiamine (a thiamine phosphorylation inhibitor); five rats never exposed to alcohol were treated with pyrithiamine; four alcohol-exposed rats were treated with thiamine; and four rats never exposed to alcohol were treated with thiamine. On day 14, thiamine was restored in all 18 rats; 2 weeks later the 10 pyrithiamine-treated rats received intraperitoneal thiamine. The rats were perfused 61 days post-pyrithiamine treatment at age 598 days. Brains were dissected and weight and volumes were calculated. Sagittal sections were stained to measure white matter structures. The corpus callosum was examined using transmission electron microscopy to determine density of myelinated fibers, fiber diameter, and myelin thickness. The corpus callosum in the alcohol/ pyrithiamine group was significantly thinner, had greater fiber density, higher percentage of small fibers, and myelin thinning than in the alcohol/thiamine and water/thiamine groups. Several measures showed a graded effect, where the alcohol/pyrithiamine group had greater pathology than the water/pyrithiamine group, which had greater pathology than the two thiamine-replete groups. Across all 16 rats, thinner myelin sheaths correlated with higher percentage of small fibers. Myelin thickness and axon diameter together accounted for 71% of the variance associated with percentage of small fibers. Significant abnormalities in the alcohol/pyrithiamine group and lack of abnormality in the alcohol-exposed/thiamine-replete group indicate that thiamine deficiency caused white matter damage. The graded abnormalities across the dually to singly treated animals support a compounding effect of alcohol exposure and thiamine depletion, and indicate the potential for interaction between alcohol and thiamine deficiency in human alcohol-related brain damage.