Mair R G, Anderson C D, Langlais P J, McEntee W J
Brain Res. 1985 Dec 23;360(1-2):273-84. doi: 10.1016/0006-8993(85)91243-0.
Several lines of evidence indicate that thiamine deficiency causes the Wernicke-Korsakoff syndrome, a human memory disorder. The present study examined behavioral deficits in rats after recovery from a bout of thiamine deficiency. Following behavioral testing, the brains were dissected into regions and assayed biochemically for levels of dopamine, norepinephrine, serotonin and the primary metabolites of these monoamines. Based on previous findings in this laboratory, we predicted that thiamine deficiency not only produces behavioral deficits but loss in catecholamines as well. Impairments were observed for a spatial delayed alternation task that had been learned prior to experimental treatment. In addition, experimental animals were impaired in their ability to acquire two novel tasks, active and passive shock avoidance, after recovery from the acute effects of thiamine deficiency. Comparable deficits were not observed for a number of reflex responses that were measured to assess the general neurological state of the animals. Biochemical analyses revealed that the concentration of norepinephrine was reduced significantly in cortex-hippocampus and olfactory bulb but not in other regions, while dopamine and serotonin levels were not altered in any brain region examined. These data demonstrate that a bout of thiamine deficiency can produce persistent deficits in brain norepinephrine and concomitant decrements in behavioral measures of learning and memory. These results are consistent with our hypothesis and evidence that noradrenergic deficits contribute to the amnesic symptoms of Korsakoff's psychosis.
多项证据表明，硫胺素缺乏会导致韦尼克 - 科尔萨科夫综合征，这是一种人类记忆障碍。本研究检测了大鼠在经历一轮硫胺素缺乏并恢复后的行为缺陷。行为测试后，将大脑解剖成不同区域，并对多巴胺、去甲肾上腺素、血清素以及这些单胺类物质的主要代谢产物水平进行生化检测。基于本实验室之前的研究结果，我们预测硫胺素缺乏不仅会导致行为缺陷，还会导致儿茶酚胺类物质减少。在实验处理前学会的空间延迟交替任务中观察到了损伤。此外，实验动物在从硫胺素缺乏的急性影响中恢复后，获取主动和被动回避电击这两项新任务的能力也受到了损害。在测量的一些反射反应中未观察到类似的缺陷，这些反射反应用于评估动物的一般神经状态。生化分析显示，去甲肾上腺素浓度在皮质 - 海马体和嗅球中显著降低，但在其他区域未降低，而在所检测的任何脑区中多巴胺和血清素水平均未改变。这些数据表明，一轮硫胺素缺乏会导致大脑去甲肾上腺素持续缺乏，并伴随学习和记忆行为指标的下降。这些结果与我们的假设一致，也证明了去甲肾上腺素能缺陷导致科尔萨科夫精神病失忆症状的证据。
