不同双环己酮草酰二腙剂量诱导小鼠行为学改变及海马CA1区和DG区内有髓神经纤维改变

李永德; 王芸; 程国华; 彭超; 陈林; 卢伟; 孔吉明; 肖岚; 唐勇

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不同双环己酮草酰二腙剂量诱导小鼠行为学改变及海马CA1区和DG区内有髓神经纤维改变

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- 不同双环己酮草酰二腙剂量诱导小鼠行为学改变及海马CA1区和DG区内有髓神经纤维改变
- Different doses of cuprizone induce mice behavior alterations and changes of myelinated nerve fibers in hippocampal CA1 and DG regions
- 陆军军医大学学报 2013年35卷第13期页码：1331-1336
- 作者机构：
- 作者简介：
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  中图分类号： R-332;R338.11;R749.15
- 纸质出版：2013
- 稿件说明：
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李永德,王芸,程国华,彭超,陈林,卢伟,孔吉明,肖岚,唐勇.不同双环己酮草酰二腙剂量诱导小鼠行为学改变及海马CA1区和DG区内有髓神经纤维改变[J].陆军军医大学学报(原第三军医大学学报),2013,35(13):1331-1336.

　Li Yongde,Wang Yun,Cheng Guohua,Peng Chao,Chen Lin,Lu Wei,Kong Jiming,Xiao Lan,Tang Yong.Different doses of cuprizone induce mice behavior alterations and changes of myelinated nerve fibers in hippocampal CA1 and DG regions[J].J Amry Med Univ (J Third Mil Med Univ),2013,35(13):1331-1336.
李永德,王芸,程国华,彭超,陈林,卢伟,孔吉明,肖岚,唐勇.不同双环己酮草酰二腙剂量诱导小鼠行为学改变及海马CA1区和DG区内有髓神经纤维改变[J].陆军军医大学学报(原第三军医大学学报),2013,35(13):1331-1336. DOI：

　Li Yongde,Wang Yun,Cheng Guohua,Peng Chao,Chen Lin,Lu Wei,Kong Jiming,Xiao Lan,Tang Yong.Different doses of cuprizone induce mice behavior alterations and changes of myelinated nerve fibers in hippocampal CA1 and DG regions[J].J Amry Med Univ (J Third Mil Med Univ),2013,35(13):1331-1336. DOI：

摘要

目的探讨双环己酮草酰二腙（cuprizone

CPZ）喂养动物模型作为精神分裂症动物模型的合适剂量和CPZ剂量、海马脱髓鞘改变和行为学改变间的关系。方法使用0.2%、0.3%、0.4%（质量分数）3种剂量CPZ喂养C57BL/6鼠6周，与控制组比较体质量、生存时间和行为学的改变情况，运用免疫组化和光密度比较各组小鼠海马CA1区和DG区内髓鞘改变情况，使用体视学方法研究0.2% CPZ组小鼠海马分区内有髓神经纤维改变情况。结果 0.4% CPZ组小鼠生存时间显著性低于控制组（

0.01），控制组、0.2% CPZ组和0.3% CPZ组的生存时间无统计学差异（

0.05）。CPZ喂养组小鼠体质量显著性低于控制组（

0.05），且剂量越高，体质量丢失越严重。0.2% CPZ组小鼠旷场实验在中央区域的活动显著性增高（

0.05）。0.2% CPZ组和0.3% CPZ组小鼠海马CA1区MBP染色的平均光密度值显著性低于控制组（

0.01），0.2% CPZ组小鼠海马DG区MBP染色的平均光密度值显著性低于控制组和0.3%CPZ组（

0.01）。控制组和0.2% CPZ组海马CA1区和DG区体积无显著性差异（

0.05）。0.2% CPZ组海马CA1区和DG区内有髓神经纤维长度密度和总长度显著性低于控制组（

0.05）。结论 0.2% CPZ为用于诱导精神分裂症动物模型的适合CPZ剂量，0.2%CPZ喂养6周可导致小鼠海马CA1和DG区内有髓神经纤维脱髓鞘。

Abstract

Objective To explore an appropriate dose of cuprizone (CPZ) for the CPZ-fed animal model as a novel schizophrenia animal model

and to investigate the possible relationship among CPZ dose

demyelination of nerve fibers in hippocampus and behavior alternations in CPZ-fed mice. Methods C57BL/6 mice

were fed with 0.2%

0.3% and 0.4% (w/w) of CPZ for 6 weeks

respectively

and the mice without any treatment were used as control. The body weight

survival time and behavior changes were compared between the CPZ-fed mice and the control mice. The myelin basic protein (MBP)-positive nerve fibers in CA1 and DG regions of hippocampus were stained with immunohistochemical methods

and the mean optical density (OD) of MBP-positive nerve fibers in the hippocampal CA1 and DG regions of each group were calculated and compared. The changes of the myelinated nerve fibers in CA1 and DG regions of hippocampus between the control group and 0.2% CPZ group were investigated with a stereological method. Results The survive time of the 0.4% CPZ group was significantly less than that of control group (

0.01). The body weight of the CPZ-fed groups was significantly lower than that of the control group (

0.05)

and the weight loss increased along with the increase of CPZ doses. In open field test

the mice fed with 0.2% of CPZ spent significantly more time in the central area of box compared with the control group (

0.05). The ODs of MBP-positive fibers in CA1 region of hippocampus in the 0.2% CPZ group and 0.3% CPZ group were significantly lower than that in the control group (

0.01). The OD of MBP-positive fibers in DG region of hippocampus in the 0.2% CPZ group was significantly lower than that in the control group and 0.3% CPZ group (

0.01). The volumes of CA1 and DG regions of the hippocampus in the 0.2% CPZ group were not significantly different from those in the control group (

0.05). The length density and total length of the myelinated nerve fibers in CA1 and DG regions of hippocampus in the 0.2% CPZ group were significantly less than those in the control group (

0.05). Conclusion 0.2% CPZ (w/w) was the appropriate dose for CPZ-fed animal model to mimic schizophrenia. The myelinated fibers in CA1 and DG regions of hippocampus undergo demyelination whe

n mice are exposed to 0.2% CPZ for 6 weeks.

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