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纸质出版:2016
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雷楚,黄嘉璐,陈昊炜,胡俊,周振华,陈康宁.双环己酮草酰二腙诱导脱髓鞘模型小鼠情绪及神经递质的变化[J].陆军军医大学学报(原第三军医大学学报),2016,38(11):1263-1269.
Lei Chu,Huang Jialu,Chen Haowei,Hu Jun,Zhou Zhenhua,Chen Kangning.Correlation between emotional changes and neurotransmitters in cuprizone-induced demyelination mice[J].J Amry Med Univ (J Third Mil Med Univ),2016,38(11):1263-1269.
雷楚,黄嘉璐,陈昊炜,胡俊,周振华,陈康宁.双环己酮草酰二腙诱导脱髓鞘模型小鼠情绪及神经递质的变化[J].陆军军医大学学报(原第三军医大学学报),2016,38(11):1263-1269. DOI:
Lei Chu,Huang Jialu,Chen Haowei,Hu Jun,Zhou Zhenhua,Chen Kangning.Correlation between emotional changes and neurotransmitters in cuprizone-induced demyelination mice[J].J Amry Med Univ (J Third Mil Med Univ),2016,38(11):1263-1269. DOI:
目的 观察双环己酮草酰二腙(cuprizone,CPZ)诱导脱髓鞘模型小鼠情绪及神经递质的变化特点,探讨髓鞘脱失和再生过程中情绪变化的可能原因。 方法 选36只C57BL/6雄性小鼠,分为3组,正常对照组予以正常饲料14周;慢性脱髓鞘组予以含0.2%CPZ粉末的饲料14周;髓鞘修复组先用含0.2%CPZ粉末的饲料12周,再换用正常饲料2周。采用LFB染色、免疫荧光及透射电镜技术观察胼胝体区髓鞘以及星形胶质细胞的变化情况;通过体质量、旷场、高架十字迷宫及悬尾实验检测小鼠行为学的变化;利用酶联免疫吸附法和高效液相色谱-电化学检测法(HPLC-ECD)测定血清肾上腺素、去甲肾上腺素、五羟色胺、多巴胺、二羟基苯乙酸和五羟基吲哚乙酸的浓度。 结果 慢性脱髓鞘组和髓鞘修复组胼胝体区髓鞘明显脱失(P0.01),两组GFAP的表达明显升高( P0.01)。慢性脱髓鞘组小鼠旷场实验总路程、中央路程及中央区活动时间均较其他2组明显减少(P0.05);在高架十字迷宫中,慢性脱髓鞘组小鼠开臂滞留时间百分比(OT%)和开臂进入次数百分比(OE%)较正常对照组减少(P0.05);慢性脱髓鞘组及髓鞘修复组小鼠在悬尾实验中的静止时间较正常对照组增加(P0.05)。HPLC-ECD及ELISA测得慢性脱髓鞘组血清NE和5-HT的浓度与正常对照组相比,差异具有统计学意义(P0.05)。 结论 CPZ诱导的脱髓鞘模型小鼠表现出焦虑、抑郁等行为变化,可能与脑组织的髓鞘脱失以及脱髓鞘环境下神经递质的含量变化有关。
Objective To observe the correlation between emotional changes and neurotransmitters in cuprizone (CPZ)-induced demyelination mice. Methods Thirty-six C57BL/6 mice were divided into 3 groups: the normal control group which was given normal diet
the chronic demyelination group which was given 0.2% CPZ mixed diet for 14 weeks
and the remyelination group which was given 0.2% CPZ diet for 12 weeks and normal diet for 2 weeks. The changes of the corpus callosum areas and astrocytes were observed by Lucas fast blue staining
immunofluorescence assay
and transmission electron microscopy. The behavior changes of the mice were detected by body weight
open field test
elevated plus maze and tail suspension test. The concentrations of monoamine neurotransmitters such as epinephrine
norepinephrine (NE)
5-hydroxytryptamine (5-HT)
dopamine
3
4-dihydroxyphenylacetic acid
and 5-hydroxyindole-3-acetic acid were measured by enzyme-linked immunosorbent assay (ELISA) and high-performance liquid chromatography-electrochemical detection (HPLC-ECD). Results The loss of myelin sheath in the corpus callosum areas of the chronic demyelination group and the remyelination group were significant (P0.01)
and the expression of glial fibrillary acidic protein (GFAP) of the both groups were increased significantly (P0.01). In open field test
the total distance
distance of central movement
and time of central movement in the demyelination group were reduced significantly (P0.05). In elevated plus maze
the percentage of open arm time (OT%) and the percentage of open arm entries (OE%) of the demyelination group were lower than those of the normal control group (P0.05). In tail suspension test
the tail hanging inactive time was increased significantly in the demyelination group and the remyelination group (P0.05) compared with the normal control group. HPLC-ECD and ELISA results showed that the concentrations of NE and 5-HT in the normal control group and the demyelination group had significant difference (P0.05). Conclusion The CPZ-induced demyelination mice have behavior changes such as anxiety and depression
which may be related with the demyelination of brain tissue and the changes of neurotransmitters.
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