Selective impairment of working memory in a mouse model of chronic cerebral hypoperfusion
Selective impairment of working memory in a mouse model of chronic cerebral hypoperfusion
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DOI：
10.1161/strokeaha.107.490151
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发表时间：
2007-10-01
期刊：
影响因子：
8.3
通讯作者：
Tomimoto, Hidekazu
中科院分区：
文献类型：
--
作者：
Shibata, Masunari;Yamasaki, Nobuyuki;Tomimoto, Hidekazu
背景和目的--我们最近设计了一种慢性脑低灌注的小鼠模型，在该模型中，大脑白质受损，但没有明显的灰质损害。方法成年C57BL/6雄性小鼠随机分为假手术组和双侧颈总动脉狭窄(BCAS)组。BCAS后30d，将70只动物随机分为3组，进行行为测试。第一组接受综合行为测试，包括神经筛查、脉冲前抑制、热板、开阔视野、明暗转换、Porsolt强迫游泳、情境和线索恐惧条件反射(BCAS n=13；假手术组n=11)。第二组为8臂径向迷宫实验的工作记忆任务(BCAS n=12，假手术组n=10)，第三组为8臂径向迷宫实验的参考记忆任务(BCAS n=13，假手术组n=11)。另一批动物进行组织学检查(BCAS n=11，假手术组n=12)。结果--脑白质稀疏，未见明显的海马区缺血性病变。对照组和BCAS小鼠在综合测试电池中没有明显的差异。然而，在用8臂径向迷宫测试的工作记忆任务中，BCAS组小鼠犯的错误明显多于对照组小鼠(P<；0.0001)。同样，在参考记忆任务中，两组之间没有可检测到的差异。结论-在BCAS后30天，小鼠的工作记忆缺陷以及脑白质变化明显。工作记忆缺陷可归因于额叶-皮质下回路的损害，这表明BCAS模型对评估皮质下血管性痴呆的底物是有用的。
Background and Purpose - We recently designed a mouse model of chronic cerebral hypoperfusion, in which the cerebral white matter is damaged without significant gray matter lesions. The behavioral characteristics of these mice were studied using a test battery for neurological and cognitive functions.Methods - Adult C57Bl/6 male mice were subjected to either sham-operation or bilateral common carotid artery stenosis (BCAS) using microcoils with an internal diameter of 0.18 mm. At 30 days after BCAS, 70 animals were divided into 3 groups and subjected to behavioral test batteries. The first group underwent comprehensive behavioral test, including the neurological screen, prepulse inhibition, hot plate, open field, light/dark transition, Porsolt forced swim and contextual and cued fear conditioning (BCAS n = 13; sham-operated n = 11). The second group was for the working memory task of the 8-arm radial maze test (BCAS n = 12; sham-operated n = 10), and the third for the reference memory task of the 8-arm radial maze test (BCAS n = 13; sham-operated n = 11). Another batch of animals were examined for histological changes (BCAS n = 11; sham-operated n = 12).Results - The white matter including the corpus callosum was consistently found to be rarefied without clear ischemic lesions in the hippocampus. No apparent differences were observed in the comprehensive test batteries between the control and BCAS mice. However, in the working memory tasks tested with the 8-arm radial maze, the BCAS mice made significantly more errors than the control mice (P < 0.0001). Again, there were no detectable differences in the reference memory tasks between the groups.Conclusions - At 30 days after BCAS, working memory deficits as well as white matter changes were apparent in the mice. Working memory deficit was attributable to damage of the frontal-subcortical circuits, suggesting the BCAS model is useful to evaluate the substrates of subcortical vascular dementia.