慢性痛伴焦虑小鼠中脑腹侧被盖区向伏隔核及腹侧海马的分支投射  

Collateral projections from the ventral tegmental area to nucleus accumbens and ventral hippocampus in mice with chronic pain and anxiety-like behavior

作　　者：马腾 姬媛媛 颜林枫[1] 李金莲 崔光彬 Ma Teng;Ji Yuanyuan;Yan Linfeng;Li Jinlian;Cui Guangbin(Department of Radiology,Functional and Molecular Imaging Key Lab of Shaanxi Province,Tangdu Hospital,Air Force Medical University,Xi’an 710038;Department of Anatomy and Histology and Embryology and K.K.Leung Brain Research Center,Preclinical School of Medicine,Air Force Medical University,Xi’an 710032;College of Forensic Medicine,Xi’an Jiaotong University,Xi’an 710061,China)

机构地区：[1]空军军医大学,唐都医院放射科暨陕西省功能与分子影像重点实验室,西安710038 [2]空军军医大学基础医学院人体解剖与组织胚胎学教研室暨梁銶琚脑研究中心,西安710032 [3]西安交通大学法医学院,西安710061

出　　处：《神经解剖学杂志》2022年第6期603-610,共8页Chinese Journal of Neuroanatomy

基　　金：国家自然科学基金(81870866);陕西省重点研发计划重点产业链项目(2019ZDLSF02-07)。

摘　　要：目的:观察小鼠中脑腹侧被盖区(VTA)多巴胺能神经元向伏隔核(NAc)及腹侧海马(vHIP)的分支投射,并为其参与慢性痛伴焦虑信息的传递提供形态学证据。方法:将实验小鼠随机分为慢性痛组(cuff)和假手术组(sham),于术后1、3、7、14 d对小鼠进行机械痛敏检测,于术后7 d采用立体定位注射方法在cuff组小鼠的左侧NAc及vHIP分别注射四甲基罗达明(TMR)和荧光金(FG),于术后14 d对小鼠进行旷场实验(OFT)、高架十字迷宫实验(EPM)检测。结合免疫荧光组织化学染色方法观察慢性痛伴焦虑小鼠中脑VTA内FG/TMR双标神经元,及酪氨酸羟化酶(TH)、FOS蛋白的表达情况。结果:(1)与sham组相比,cuff组小鼠术后第1 d就出现了机械痛阈的降低,并一直持续至第14 d,而且呈现出明显的焦虑样情绪反应;(2)慢性痛伴焦虑小鼠中脑VTA内有部分神经元为FG/TMR双标神经元,大约有(58.19±7.67)%及(76.40±0.67)%的FG/TMR双标神经元分别表达FOS及TH。结论:小鼠中脑VTA内多巴胺能神经元可以同时向NAc及vHIP发出分支投射,其中部分分支投射神经元可能参与了慢性痛伴焦虑信息的传递。Objective:To explore whether the ventral tegmental area(VTA)dopaminergic neurons send collateral projections to the nucleus accumbens(NAc)and ventral hippocampus(vHIP),and provide evidence for collateral VTA projection neurons involved in chronic pain and anxiety comorbidity.Methods:Mice were randomly divided into chronic pain and sham groups.Mechanical allodynia was tested at 1th,3th,7th,and 14th day after cuffing operation.Mice in cuff group were stereotactically injected with tetramethylrhodamine-dextran(TMR)into the left NAc and Fluoro-gold(FG)into the left vHIP at 7th day after cuffing operation.Open field test(OFT)and elevated plus-maze test(EPM)were performed to test the anxiety-like behavior at 14th after cuffing operation.Combining the immunofluorescence histochemical staining method,the FG/TMR double-labeled neurons,FG/TMR/FOS,and FG/TMR/TH triple-labeled VTA neurons were observed in mice with chronic pain and anxiety-like behavior.Results:(1)Compared with the sham group,mice in cuff group showed mechanical allodynia at 1th day after cuffing operation,which last until 14th day.And mice in cuff group showed anxiety-like behavior at 14th day;(2)Some VTA neurons were FG/TMR double-labeled neurons in mice with chronic pain and anxiety-like behavior.About(58.19±7.67)%and(76.40±0.67)%FG/TMR double-labeled VTA neurons were FG/TMR/FOS and FG/TMR/TH triple-labeled neurons.Conclusions:Mice VTA dopaminergic neurons can send collateral projections to the NAc and vHIP.Some collateral VTA projection neurons may be involved in chronic pain and anxiety comorbidity.

关 键 词：慢性痛 焦虑 中脑腹侧被盖区 伏隔核 腹侧海马 酪氨酸羟化酶 小鼠 

分 类 号：R338[医药卫生—人体生理学]