Langlais P J, Savage L M
Neurology Research Service (127), VA Medical Center, San Diego, CA 92161, USA.
Behav Brain Res. 1995 Apr;68(1):75-89. doi: 10.1016/0166-4328(94)00162-9.
Exploratory activity, spontaneous alternation, learning and memory abilities were examined in the pyrithiamine-induced thiamine deficiency (PTD) rat model of Wernicke-Korsakoff's syndrome and pair-fed controls (CT). PTD and CT animals showed normal retention of a single trial of a passive avoidance task acquired prior to the acute stages of thiamine deficiency. While there were no significant group differences in spontaneous activity, PTD animals with extensive damage to internal medullary lamina (IML-lesioned) of thalamus and mammillary body nuclei demonstrated a significant decrease in spontaneous alternation and were significantly impaired in learning both the initial spatial non-matching-to-position (NMTP) task and the reverse MTP task. PTD animals without IML damage (IML-spared) were only impaired on the acquisition of NMTP. Examination of response patterns suggest that the learning impairment was related to an inability to adopt or shift to the appropriate response rule. Performance of PTD IML-lesioned animals on NMTP mixed-delay sessions (4, 30, 60, 90 s) was similar to controls and PTD IML-spared, but was significantly lower on MTP delay trials. These IML-lesioned rats also had significant reductions in thickness of frontal and parietal cortex, corpus callosum and severe neuronal loss in anterior and reticular thalamic nucleic. Four PTD IML-lesioned animals that were unable to learn the NMTP task had more extensive cortical, white matter and thalamic damage than the PTD IML-lesioned animals that did learn the task. These results demonstrate that thiamine deficiency in the rat produces behavioral changes ranging from mild cognitive deficits to severe learning and memory impairments. Pathologic damage following a bout of thiamine deficiency also varies from neuronal loss in select thalamic nuclei to tissue loss in large regions of thalamus, mammillary bodies and cortex. Learning and memory deficits are closely related to the degree of cortical and diencephalic damage.
在硫胺素缺乏诱导的韦尼克-科尔萨科夫综合征（Wernicke-Korsakoff syndrome）大鼠模型和配对喂养对照组（CT）中，检测了探索活动、自发交替、学习和记忆能力。硫胺素缺乏诱导（PTD）组和CT组动物在硫胺素缺乏急性期之前获得的单次被动回避任务的记忆保持正常。虽然自发活动方面两组无显著差异，但丘脑内髓板（IML）和乳头体核广泛受损的PTD动物自发交替显著减少，并且在学习初始空间位置不匹配（NMTP）任务和反向MTP任务时均显著受损。无IML损伤的PTD动物（IML未受损）仅在NMTP获取方面受损。对反应模式的检查表明，学习障碍与无法采用或转换到适当的反应规则有关。PTD IML损伤动物在NMTP混合延迟实验（4、30、60、90秒）中的表现与对照组和PTD IML未受损组相似，但在MTP延迟试验中的表现显著较低。这些IML损伤大鼠的额叶和顶叶皮质、胼胝体厚度也显著降低，丘脑前核和网状核有严重的神经元丢失。四只无法学习NMTP任务的PTD IML损伤动物比能够学习该任务的PTD IML损伤动物有更广泛的皮质、白质和丘脑损伤。这些结果表明，大鼠硫胺素缺乏会产生从轻度认知缺陷到严重学习和记忆障碍的行为变化。一次硫胺素缺乏后的病理损伤也有所不同，从特定丘脑核团的神经元丢失到丘脑、乳头体和皮质大片区域的组织丢失。学习和记忆缺陷与皮质和间脑损伤程度密切相关。
