吉林大学学报(医学版) ›› 2016, Vol. 42 ›› Issue (03): 473-480.doi: 10.13481/j.1671-587x.20160311

• 基础研究 • 上一篇    下一篇

外侧缰核中5-HT2C受体在帕金森病模型大鼠焦虑行为中的调节作用及其机制

韩玲娜1, 王春雷2, 张莉3   

  1. 1. 长治医学院生理学教研室, 山西 长治 046000;
    2. 长治医学院生物医学工程系, 山西 长治 046000;
    3. 西安交通大学医学部生理学与病理生理学系, 陕西 西安 710061
  • 收稿日期:2015-10-29 发布日期:2016-06-17
  • 通讯作者: 张莉,副教授,硕士研究生导师(Tel:029-82657490-829,E-mail:zhangli1998@mail.xjtu.edu.cn) E-mail:zhangli1998@mail.xjtu.edu.cn
  • 作者简介:韩玲娜(1981-),女,山西省长治市人,讲师,理学博士,主要从事帕金森病的神经机制方面的研究。
  • 基金资助:

    陕西省科技厅国际合作与交流计划项目资助课题(2015KW-040);长治医学院科技创新团队项目资助课题(CX201506)

Regulatory effects of 5-HT2C receptors in lateral habenular nucleus on anxiety behaviors in rat models of Parkinson's disease and their mechanisms

HAN Lingna1, WANG Chunlei2, ZHANG Li3   

  1. 1. Department of Physiology, Changzhi Medical College, Changzhi 046000, China;
    2. Department of Bioengineering, Changzhi Medical College, Changzhi 046000, China;
    3. Department of Physiology and Pathophysiology, School of Medical Sciences, Xi'an Jiaotong University, Xi'an 710061, China
  • Received:2015-10-29 Published:2016-06-17

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摘要：

目的: 探讨外侧缰核(LHb)中5-羟色胺2C(5-HT2C)受体在调节帕金森病(PD)大鼠相关焦虑行为中的作用,阐明PD相关焦虑行为的神经机制。方法: 将126只大鼠随机分为假手术组(n=63)和黑质致密部(SNc)损毁组(n=63)。采用行为学方法观察2组大鼠在旷场实验中的中央区停留时间百分比、高架十字迷宫实验(EPM)中的开放臂进入次数百分比和开放臂停留时间百分比;采用高效液相色谱-电化学检测法观察大鼠边缘相关脑区中单胺类递质水平;采用组织学和免疫组织化学染色法确认套管位置及SNc损毁后多巴胺(DA)神经元的缺失程度。结果: 与假手术组比较,SNc损毁组大鼠中央区停留时间百分比(F1,72=36.678,P<0.001)、开放臂进入次数百分比(F1,72=59.077,P<0.001)和开放臂停留时间百分比(F1,72=84.245,P<0.001)均明显降低,且内侧前额叶皮层(mPFC)(P<0.01)、杏仁核(P<0.01)和海马(P<0.05)中DA水平均明显下降;LHb中局部注射5-HT2C受体激动剂Ro60-0175后,与未加入Ro60-0175时比较,2组大鼠中央区停留时间百分比(P<0.05或P<0.01)、开放臂进入次数百分比(P<0.05或P<0.01)和开放臂停留时间百分比(P<0.05或P<0.01)均明显降低;且mPFC、杏仁核和海马中3种单胺类递质DA、5-HT和去甲肾上腺素(NA)水平均不同程度下降。在mPFC,2组大鼠给予Ro60-0175后,3种递质水平均明显降低(P<0.05或P<0.01);在杏仁核,给予Ro60-0175后,除5-HT水平无明显变化外,其余2种递质水平明显下降(P<0.05或P<0.01);在海马,给予Ro60-0175后,除假手术组大鼠NA水平无变化外,其余均明显下降(P<0.05或P<0.01)。组织学确认行为学实验中使用大鼠套管均位于LHb上方1mm;免疫组织化学检测,SNc损毁组大鼠损毁侧SNc中DA神经元完全缺失,且腹侧被盖区DA神经元较未损毁侧明显减少(P<0.001)。结论: LHb中5-HT2C受体的激活可诱发或增强大鼠的焦虑行为,其机制与相关脑区中单胺类递质水平变化有关联。

关键词: 帕金森病, 焦虑, 外侧缰核, 5-HT2C受体

Abstract:

Objective: To study the effects of 5- hydroxytryptamine 2C(5-HT2C) receptors in the lateral habenular nucleus(LHb) on anxiety behaviors in the rats with Parkinson's disease(PD),and to clarify the neural mechanisms of PD associated anxiety behaviors. Methods: A total of 126 rats were randomly divided into sham operation group (n= 63) and substantia nigrapar compacta(SNc) lesion group(n=63).The anxiety behaviors of rats in two groups such as the percentges of the time spending in center region were observed by the open field test,and the percentages of number of open arm entries and time of open arm staying were observed by elevated plus maze test;the monoamine levels in limbic related brain regions were assessed by high performance liquid chromatography with electrochemical detection;the cannula position and the degeneration of dopamine (DA) neurons after SNc lesion were confirmed by histological and immunohistochemical staining. Results: Compared with sham operation group, the percentage of time spending in center region (F1,72 = 36.678,P<0.001),the percentage of number of open arm entries (F1,72 = 59.077,P<0.001) and the percentage of time of open arm staying (F1,72 = 84.245,P<0.001) of the rats in SNc lesion group were decreased.The DA levels in medial prefrontal cortex (mPFC) (P<0.01),amygdala (P<0.01),and hippocampus (P<0.05) of the rats in SNc lesion group were significantly decreased compared with sham operation group. Compared with the rats treated with vehicle in the same group, the intra-injection of 5-HT2C receptors agonist Ro60-0175 could significantly decrease the percentages of time spending in center region(P<0.01 or P<0.01),the percentages of number of open arm entries (P<0.05 or P<0.01),and the percentages of time of open staying(P<0.05 or P<0.01) and the monoamine levels in mPFC,amygdala and hippocampus of the rats.Three monoamine levels in mPFC of the rats in two groups were decreased significantly (P<0.05 or P<0.01);in amygdala,the DA and NA levels of rats in two groups were decreased significantly (P<0.05 or P<0.01);in hippocampus,all the monoamine levels except for the NA levels of the rats in sham operation group were significantly reduced(P<0.05 or P<0.01);the behavioral test results showed that the cannula position of rats was located at 1 mm above the LHb.The immunohistochemical staining results showed that the DA neurons of the injected side of the rats in SNc lesion group were missing,and the number of DA neurons in ventral tegmetal area was lower than that in unSNc area(P<0.001). Conclusion: The anxiety-like behaviors can be induced or enhanced after activation of LHb 5-HT2C receptors,and their mechanisms may involve the changes of monoamine levels in the related brain regions.

Key words: Parkinson's disease, anxiety, lateral habenular nucleus, 5-HT2C receptor

中图分类号: 

  • R338.8
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