PD大鼠模型的行为学评价和黑质-纹状体通路中单胺类神经递质的含量变化

doi:10.13418/j.issn.1001-165x.2015

中国临床解剖学杂志 ›› 2015, Vol. 33 ›› Issue (2): 182-188.doi: 10.13418/j.issn.1001-165x.2015

PD大鼠模型的行为学评价和黑质-纹状体通路中单胺类神经递质的含量变化

陆小军¹,　谢志颖², 　付星卉²,　翟万庆¹, 　夏春林²

1. 太仓市第一人民医院，江苏太仓 215400； 2. 苏州大学医学部博习临床解剖学研究所，江苏苏州 215123

收稿日期:2014-09-01 出版日期:2015-03-25 发布日期:2015-04-21
通讯作者: 翟万庆，主任医师，E-mail: zhaiwanqingg@21cn.com 夏春林，教授，博士生导师，E-mail: xclcnb@suda.edu.cn E-mail:1130506021@suda.edu.cn
作者简介:共同第一作者：陆小军(1972-), 男，江苏太仓人，研究方向：神经系统退行性疾病诊断与治疗，E-mail: luxiaojun5215@163.com；谢志颖(1994-)，男，江苏淮安人，研究方向：神经系统退行性疾病发病机制，E-mail: 1130506021@suda.edu.cn
基金资助:
江苏省卫生厅科技项目(YG201307)

Behavioral evaluation and changes in levels of monoamine neurotransmitter within the nigrostriatal pathway in rat models of Parkinson's disease

LU Xiao-jun¹, XIE Zhi-ying², FU Xing-hui², ZHAI Wan-qing¹, XIA Chun-lin²

1. First People’s Hospital of Taicang, Taicang 215400, Jiangsu Province，China; 2. Boxi Institute of Clinical Anatomy, Medical College of Soochow University, Suzhou 215123, Jiangsu Province，China

Received:2014-09-01 Online:2015-03-25 Published:2015-04-21

摘要/Abstract

摘要：

目的　建立帕金森病(Parkinson’s disease, PD)大鼠模型，观测和评价其行为学改变，检测和分析PD大鼠模型黑质-纹状体通路中单胺类神经递质含量变化。方法　采用6-羟基多巴胺立体定向注射至成年SD大鼠单侧前脑内侧束，制作偏侧PD大鼠模型，观测和评价其行为学改变(悬尾测试、旋转行为的旋转速度、启动时间和维持时间)，通过高效液相色谱法测定和分析单胺类神经递质的含量在PD大鼠模型黑质-纹状体通路中的变化。结果　(1) PD大鼠出现了尾僵直、少动、运动迟缓、震颤、竖毛、咬尾或足、姿势和步态不稳等异常行为；(2) 悬尾测试对于评价PD模型没有统计学意义，旋转行为的旋转速度、启动时间和维持时间的结果具有统计学意义且呈时间依赖性；(3) PD大鼠模型毁损侧的黑质与纹状体部位的多巴胺(Dopamine, DA)和五羟色胺(Serotonin, 5-HT)含量均降低，DA的含量具有逐渐下降的趋势，术后第2、3、4及5周黑质部位的DA含量相对于正常对照组分别下降62.96%、82.88%、92.71%、91.50%，纹状体部位的DA含量分别下降77.47%、 91.39%、96.25%、96.18%；术后第3、4及5周黑质部位的DA含量平均下降(89.03±5.36)% (第3、4及5周的DA含量无统计学差异)，纹状体部位的DA含量平均下降(93.61±2.79)% (第3、4及5周的DA含量无统计学差异)。结论　(1) PD大鼠模型具有类似人类PD的运动症状，除旋转速度作为旋转行为经典的行为学指标外，启动时间和维持时间可作为PD模型旋转行为的辅助指标；(2) PD大鼠脑内毁损侧的黑质和纹状体部位的DA和5-HT含量均降低。

关键词: 帕金森病, 大鼠模型, 行为学, 黑质-纹状体通路, 单胺类神经递质

Abstract:

Objective To study the changes in levels of monoamine neurotransmitter within the nigrostriatal pathway and evaluate the behavioral changes in rat models of Parkinson's disease. Method The unilateral rat models of PD were established by injecting 6-OHDA into the right medial forebrain bundle of adult Sprague-Dawley rats. After establishing the successful rat models, we observed their abnormal behavior and evaluated the behavioral changes (elevated body swing test, average velocity, actuation time and time length of rotation behavior). Additionally, we assayed the levels of monoamine neurotransmitter in the nigrostriatal pathway of PD rats by high performance liquid chromatography. Results (1) PD rats demonstrated some abnormal behavior such as stiffness of tail, akinesia or bradykinesia, tremor and the instable posture and gait, etc. (2) Statistically, elevated body swing test was not significant for the evaluation of PD rat models, while average velocity, actuation time and time length of rotation behavior were significant for the evaluation and showed a time-dependent pattern. (3) Both of the content of DA and serotonin were reduced in the substantia nigra and the striatum of the pathological lateral in PD rats, and the DA content decreased with time; Moreover, the degree of decline in DA content of the substantia nigra were respectively 62.96%, 82.88%, 92.71% and 91.50% and the striatum were respectively 77.47%, 91.39%, 96.25% and 96.18% during the second week, third week, fourth week and the fifth week. The average degree of decline in DA content of the substantia nigra was (89.03±5.36)% during the third week, fourth week and the fifth week by statistical analysis, while the striatum was (93.61±2.79)%. Conclusions (1) PD rats have the human-like clinical motor symptoms of PD, and the classic behavioral evaluation index of rotational behavior is average velocity, while actuation time and time length of rotation behavior play a supporting role in behavior evaluation of PD rat models; (2) There is a decline in the content of DA and serotonin of the substantia nigra and the striatum in the lesioned lateral of PD rats.

Key words: Parkinson's disease, Rat Models, Behavior, Nigrostriatal pathway, Monoamine neurotransmitter

中图分类号:

R322.81

陆小军, 谢志颖, 付星卉, 翟万庆, 夏春林. PD大鼠模型的行为学评价和黑质-纹状体通路中单胺类神经递质的含量变化[J]. 中国临床解剖学杂志, 2015, 33(2): 182-188.

LIU Xiao-Jun, XIE Zhi-Ying, FU Xing-Hui, DI Mo-Qiang, JIA Chun-Lin. Behavioral evaluation and changes in levels of monoamine neurotransmitter within the nigrostriatal pathway in rat models of Parkinson's disease[J]. Chinese Journal Of Clinical Anatomy, 2015, 33(2): 182-188.

参考文献

[1] Spillantini MG, Crowther RA, Jakes R, et al. Alpha-Synuclein in filamentous inclusions of Lewy bodies from Parkinson's disease and dementia with lewy bodies
[J]. Proc Natl Acad Sci USA, 1998, 95(11): 6469-6473.

[2] Vernon AC. Mice with Reduced Vesicular Monoamine Storage Content Display Nonmotor Features of Parkinson's Disease
[J]. J Neurosci, 2009, 29(41): 12842-12844.

[3] Lelieveld IM, Müller ML, Bohnen NI, et al. The role of serotonin in sleep disordered breathing associated with Parkinson disease: a correlative
[11C]DASB PET imaging study
[J]. PLoS One, 2012, 7(7): e40166.

[4] Paxinos G, Watson C. The Rat Brain in Stereotaxic Coordinates
[M]. 6th ed. San Diego: Academic Press 2007.

[5] Esmaeili MH, Movahedi M, Faraji A, et al. Intracerebral injection of low amounts of norharman induces moderate Parkinsonism-like behavioral symptoms in rat
[J]. Neurotoxicol Teratol, 2012, 34(5): 489-494.

[6] Riddibough G. Homing in on the homeobox
[J]. Nature, 1992, 357(6380): 643-645.

[7] Rodriguez-Oroz MC, Jahanshahi M, Krack P, et al. Initial clinical manifestations of Parkinson’s disease: features and pathophysiological mechanisms
[J]. Lancet Neurol, 2009, 8(12): 1128-1139.

[8] Yuan H, Sarre S, Ebinger G, et al. Histological, behavioural and neurochemical evaluation of medial forebrain bundle and striatal 6-OHDA lesions as rat models of Parkinson's disease
[J]. J Neurosci Methods, 2005, 144(1): 35-45.

[9] Obeso JA, Rodríguez-Oroz MC, Benitez-Temino B, et al. Functional organization of the basal ganglia: therapeutic implications for Parkinson’s disease
[J]. Mov Disord 2008, 23 (suppl 3): S548-S559.

[10] Chaudhuri KR, Schapira AH. Non-motor symptoms of Parkinson's disease: dopaminergic pathophysiology and treatment
[J]. Lancet Neurol, 2009, 8(5): 464-474.

[11] Devanarayana NM, Rajindrajith S. Association between constipation and stressful life events in a cohort of Sri Lankan children and adolescents
[J]. J Trop Pediatr, 2010, 56(3): 144-148.

[12] Taylor TN, Caudle WM, Shepherd KR, et al. Nonmotor symptoms of Parkinson’s disease revealed in an animal model with reduced monoamine storage capacity
[J]. J Neurosci, 2009, 29(25): 8103-8113.

PD大鼠模型的行为学评价和黑质-纹状体通路中单胺类神经递质的含量变化

Behavioral evaluation and changes in levels of monoamine neurotransmitter within the nigrostriatal pathway in rat models of Parkinson's disease

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 7

Metrics

本文评价

推荐阅读 0

[1]	丁旭, 殷紫, 邓祥敏, 张艳军, 宋晓莉. 银杏内酯B对帕金森病模型大鼠的保护作用[J]. 中国临床解剖学杂志, 2022, 40(4): 442-446.
[2]	何鑫, 杨文强, 李宗泽, 于露, 赵艳, 鲁美丽, 杨菁. 肌肽对糖尿病肾病大鼠氧化应激及NF-κB信号通路的影响[J]. 中国临床解剖学杂志, 2020, 38(3): 289-294.
[3]	田荆华,朱明慧,张争辉,于兰. 帕金森病猴模型生化指标及肾上腺的改变[J]. 中国临床解剖学杂志, 2019, 37(1): 51-54.
[4]	张毅敏,连辉,付升旗,任同明,蔡君艳,王志勇. 6-羟多巴损伤黑质导致室旁核离子钙接头蛋白表达变化[J]. 中国临床解剖学杂志, 2017, 35(2): 188-192.
[5]	王晓巍,崔宏福,姚素艳,刘建生,郑德宇. 左旋多巴治疗前后帕金森大鼠脑内γ-氨基丁酸 A受体的变化[J]. 中国临床解剖学杂志, 2015, 33(6): 677-680.
[6]	曹健, 王瑞, 王倩, 王爽. 维生素C对MPP+致帕金森病细胞模型中PC12细胞凋亡的影响[J]. 中国临床解剖学杂志, 2013, 31(4): 453-456.
[7]	肖春苟, 沈伟哉, 郭国庆, 李校堃. Mrh-aFGF对帕金森病大鼠黑质神经元的保护[J]. 中国临床解剖学杂志, 2010, 28(3): 312-.