双环己酮草酰二腙诱导精神分裂症小鼠模型胼胝体有髓神经纤维脱髓鞘的定量观测  

Quantitation of demyelination in corpus callosum of CPZ-induced mouse model of schizophrenia

作　　者：程国华[1,2] 彭超[1,2] 李永德[1,2] 王芸[1,2] 陈林[1,2] 卢伟[1,2] 孔吉明[3] 肖岚[4] 唐勇[1,2] 

机构地区：[1]重庆医科大学基础医学院人体解剖与组织胚胎教研室,400016 [2]重庆医科大学干细胞与组织工程研究室,400016 [3]加拿大曼尼托巴大学人体解剖与细胞科学系 [4]第三军医大学基础医学部组织与胚胎学教研室重庆市神经科学研究所,400038

出　　处：《第三军医大学学报》2013年第7期598-603,共6页Journal of Third Military Medical University

基　　金：国家自然科学基金(31271288,81171238);重庆市“百名学术学科领军人才”培养计划(2012)~~

摘　　要：目的进一步研究双环己酮草酰二腙(cuprizone,CPZ)诱导精神分裂症动物模型胼胝体内有髓神经纤维的改变及与行为学改变之间的关系。方法 19只雄性C57BL/6小鼠被分为2组,空白对照组(n=10)和CPZ处理组(n=9),分别给予正常鼠饲料和混有0.2%(质量分数)CPZ的鼠饲料6周,运用旷场实验、高架十字迷宫实验、Morris水迷宫实验、探孔实验和转棒实验检测小鼠的行为学改变,运用免疫组化、透射电镜、体视学方法研究小鼠的胼胝体和其内有髓神经纤维的改变。结果 CPZ处理组小鼠在行为学实验中表现为:旷场实验中央区活动增多,高架十字迷宫开臂内活动增加(P<0.05),提示CPZ处理小鼠的焦虑行为减少;学习记忆能力、运动能力和基本探索行为并未受到影响(P>0.05)。透射电镜研究发现CPZ模型小鼠胼胝体存在有髓神经纤维脱髓鞘改变。透射电镜和体视学研究发现,CPZ模型小鼠胼胝体体积[(12.66±1.07)mm3]较空白对照组[(13.53±2.79)mm3]无显著性下降(P>0.05),但CPZ模型小鼠胼胝体有髓神经纤维长度密度和总长度[(0.70±0.17)km/mm3和(9.06±2.56)km]均较空白对照组[(1.47±0.17)km/mm3和(19.75±3.70)km]显著下降(P<0.05)。结论 CPZ模型可以出现类似精神分裂症样症状且胼胝体内有髓神经纤维存在脱髓鞘改变。Objective To investigate the changes of the myelinated fibers in the corpus callosum of the cuprizone （CPZ）-induced mouse model of schizophrenia, and the relationship between the demyelination changes and the behavioral abnormalities in this animal model. Methods Nineteen male C57BL/6 mice were randomly divided into 2 groups, control group （n = 10） and CPZ-treated group （n =9）. The mice in the later group were fed with a diet of 0.2% （w/w） CPZ mixed into standard rodent chow for 6 weeks. The mice in con- trol group were fed standard lab chow and lab water. The behavioral changes of the animals were investigated with a series of behavioral tests. The changes of the corpus callosum and the myelinated fibers in the corpus callosum were studied with immunohistochemical assay, transmission electron microscopy and stereological methods. Results The CPZ-treated mice displayed more activities in the central area of open field （P 〈 0. 05 ）and in the open arms of elevated plus maze（ P 〈 0.05 ）, which suggested that the anxiety behavior in the CPZ-treated mice was reduced when compared to the control. Morris water maze demonstrated that there was no working memory deficit in the CPZ-treated mice compared to the control（P 〉 0.05 ）. There was no abnormality in the motor function and basic exploration ability in the CPZ-treated mice when compared to the control. There were demyelination changes in the corpus eallosum of the CPZ-treated mice. There was no significant difference in the total volume of the corpus callosum between the CPZ-treated mice and the control（ 12.66 ± 1. 07 vs 13.53 ±2. 79 mm3 ）. The length density and total length of the myelinated fibers in the corpus callosum were significantly decreased in CPZ-treated mice than control mice（0. 70 ±0.17 vs 1.47 ±0.17 kin/ram3, 9.06±2.56 vs 19.75 ±3.70 km, P 〈 0. 05）. Conclusion change in the corpus callosum. CPZ-treated mice display schizophrenia-like behaviors and demyelination

关 键 词：双环己酮草酰二腙 精神分裂症 行为学实验 胼胝体 脱髓鞘 体视学 

分 类 号：R-332[医药卫生] R338.11