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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 further investigate the changes of myelinated nerve fibers in corpus callosum induced by cuprizone (CPZ) induced animal model of schizophrenia and its relationship with behavioral changes. Methods Nineteen male C57BL / 6 mice were divided into two groups. The blank control group (n = 10) and CPZ treatment group (n = 9) were given normal rat diet and 0.2% (mass fraction) Animals were sacrificed for 6 weeks. The open-field test, the elevated plus-maze test, the Morris water maze test, the probe test and the rotarod test were used to detect the behavioral changes in mice. Immunohistochemistry, transmission electron microscopy and stereological methods were used to study the effects of The corpus callosum and alterations of myelinated nerve fibers therein. Results In behavioral experiments, CPZ-treated mice showed increased activities in the central open-field and increased activities in the elevated plus-maze open arms (P <0.05), suggesting that the CPZ-treated mice reduced their anxiety behaviors. Learning and memory abilities, Exercise ability and basic exploration behavior were not affected (P> 0.05). Transmission electron microscopy revealed that there was demyelination of myelinated fibers in the corpus callosum of CPZ mice. Transmission electron microscopy and stereological studies showed that the volume of the corpus callosum in CPZ model mice [(12.66 ± 1.07) mm3] was significantly lower than that in the blank control group [(13.53 ± 2.79) mm3] (P <0.05) The length density and total length of myelinated nerve fibers in the corpus callosum [(0.70 ± 0.17) km / mm3 and (9.06 ± 2.56) km] were significantly higher than those in the blank control group [(1.47 ± 0.17) km / mm3 and (19.75 ± 3.70) km] Decreased (P <0.05). Conclusion The CPZ model can show symptoms similar to schizophrenia and the demyelination of myelinated nerve fibers in the corpus callosum.