摘要
目的:探讨内侧前额叶皮质(mPFC)的边缘前皮质(PrL)区5-羟色胺受体4(5-HTR4)在帕金森病(PD)大鼠焦虑样行为中的作用,阐明PD大鼠相关焦虑行为的可能神经机制。方法:320只雄性SD大鼠随机分为假手术组和盐酸6-羟基多巴(6-OHDA)毁损组[内侧前脑束(MFB)注射6-OHDA制备大鼠PD模型],每组160只。采用旷场实验和高架十字迷宫实验评测PrL区局部给予5-HTR4激动剂BIMU8或5-HTR4拮抗剂GR1138082组大鼠的焦虑行为;采用免疫组织化学染色法观察大鼠黑质致密部(SNc)和腹侧被盖区(VTA)多巴胺(DA)神经元缺失程度,计算酪氨酸羟化酶免疫反应(TH-ir)阳性神经元百分率,高压液相色谱法检测大鼠焦虑相关脑区的单胺类神经递质水平。结果:与假手术组比较,6-OHDA毁损组大鼠在旷场实验中的中央区停留时间百分比明显降低(P<0.01),在高架十字迷宫实验中开放臂进入次数百分比和开放臂停留时间百分比明显降低(P<0.05或P<0.01)。与给药前比较,PrL区给予BIMU8或GR113808后,假手术组大鼠在旷场实验中的中央区停留时间百分比、高架十字迷宫实验中开放臂进入次数百分比和开放臂停留时间百分比差异无统计学意义(P>0.05);而6-OHDA毁损组大鼠在旷场实验中的中央区停留时间百分比均明显升高(P<0.01),高架十字迷宫实验中开放臂进入次数百分比和开放臂停留时间百分比均明显升高(P<0.05或P<0.01)。与假手术组比较,6-OHDA毁损组大鼠损毁侧SNc和VTA区脑组织中TH-ir阳性神经元百分率明显降低(P<0.01),毁损侧的纹状体、mPFC、杏仁核(Amy)和腹侧海马(vHip)脑组织中单胺类神经递质水平明显降低(P<0.01)。结论:激活或阻断mPFC的PrL区5-HTR4均可改善PD大鼠相关的焦虑样行为。
Objective:To investigate the role of 5-hydroxytryptamine receptor 4(5-HTR4)in the prelimic cortex(PrL)region of media prefrontal cortex(mPFC)in anxiety behaviors of the rats with Parkinson’s disease(PD).Methods:A total of 320 male SD rats were randomly divided into sham operation group(n=160)and 6-hydroxydopamine(6-OHDA)lesion group(n=160).The rats in 6-OHDA lesion group were injected with 6-OHDA in the media forebrain bundle(MFB).The anxiety behaviors of the rats in two groups after treated with 5-HTR4 agonist BIMU8 and 5-HTR4 antagonist GR113808 in PrL region were evaluated using open field test and elevated plus-maze test.The extents of dopamine(DA)neuron loss in the substantia nigra(SNc)and ventral tegmental area(VTA)of the rats were observed by immunohistochemistry,and the percentage of tyrosineny droxylase immunoreaction(TH-ir)positive neurons was calculated.The levels of monoamine neurotransmitters in the anxiety-related brain regions were tested by reverse-phase high performance liquid chromatography.Results:Compared with sham operation group,the percentage of time spent in the central area in the open-field test in 6-OHDA lesion group was decreased(P<0.01),and the percentages of open arm entries and open arm time in the elevated plus-maze test were significantly decreased(P<0.05 or P<0.01).Compared with before injection,in sham operation group,after injection of BIMU8 or GR113808 in PrL region,the percentage of time spent in the central area in the open field test and the percentages of opern arm entries and open arm time in the elevated plus-maze test of the rats in 6-OHDA lesion group had no significant differences(P>0.05);the percentage of time spent in the central area in the open-field test and the percentages of open arm entries and open arm time in the elevated plus maze test in 6-OHDA lesion group were signisicantly increased(P<0.05 or P<0.01).Compared with sham operation group,the percentage of TH-ir positive neurons in the SNc and VTA of the injured sides of the rats in 6-OHDA lesion group wa
作者
刘怡玮
麻焕玉
高凤
王兆龙
侯曜林
崔晨凯
武星
李立博
张莉
LIU Yiwei;MA Huanyu;GAO Feng;WANG Zhaolong;HOU Yaolin;CUI Chenkai;WU Xing;LI Libo;ZHANG Li(Department of Physiology and Pathophysiology,School of Medical Sciences,Xi’an Jiaotong University,Xi’an 710061,China;Department of Rehabilitation Medicine,Second Affiliated Hospital,Xi’an Jiaotong University,Xi’an 710004,China)
出处
《吉林大学学报（医学版）》
CAS
CSCD
北大核心
2021年第1期25-34,共10页
Journal of Jilin University：Medicine Edition
基金
国家自然科学基金青年基金项目(81701259)
陕西省科技厅自然科学基金面上项目(2019JM-439)。
