腹侧被盖区多巴胺能神经元调控LPS处理小鼠的焦虑样行为  

Dopaminergic neurons in the ventral tegmental area regulate the anxiety-like behaviors in LPS-treated mice

作　　者：井思琪 仝坤 王德娟 Jing Siqi;Tong Kun;Wang Dejuan(Research Center for Biochemistry and Molecular Biology,Xuzhou Medical University,Xuzhou 221004,China;Jiangsu Key Laboratory of Anesthesiology,Xuzhou Medical University,Xuzhou 221004,China)

机构地区：[1]徐州医科大学生物化学与分子生物学研究中心,徐州221004 [2]徐州医科大学江苏省麻醉学重点实验室,徐州221004

出　　处：《神经解剖学杂志》2022年第5期485-490,共6页Chinese Journal of Neuroanatomy

基　　金：江苏省自然科学基金(BK20170260)。

摘　　要：目的:通过激活腹侧被盖区(VTA)多巴胺能神经元后观察脂多糖(LPS)处理小鼠焦虑样行为的变化,探讨小鼠VTA多巴胺能神经元对LPS处理小鼠焦虑样行为的调控作用。方法:成年雄性C57小鼠随机分为对照组(control)和LPS组,LPS组为按照100μg/kg腹腔注射脂多糖。1 d后进行旷场实验和高架十字迷宫实验检测小鼠的焦虑情绪。免疫组织荧光染色观察两组小鼠VTA区胶质纤维酸性蛋白(GFAP)和c-Fos表达。成年雄性DAT-cre小鼠随机分为两组,即LPS组与LPS+化学遗传组,LPS造模前3周LPS组双侧VTA注射rAAV-DIO-mCherry病毒;LPS+化学遗传组双侧VTA注射rAAV-DIO-hM3Dq-mCherry病毒,造模1 d后两组小鼠腹腔注射N-氧化氯氮平(CNO),30 min后进行旷场实验和高架十字迷宫实验。结果:旷场实验中,LPS组小鼠进入中央区域的距离与对照组相比明显减少(P<0.05),而运动距离无统计学差异(P>0.05)。高架十字迷宫实验中,LPS组小鼠在进入开放臂的探索时间与对照组比明显减少(P<0.05)。与对照组相比,LPS组小鼠脑内VTA区GFAP表达上调,c-Fos表达下降;化学遗传结果显示,与LPS组相比,激活小鼠VTA区多巴胺能神经元后LPS小鼠进入旷场中央区域的距离与进入高架十字迷宫开臂时间明显增加(P<0.05)。结论:LPS处理的小鼠VTA区星形胶质细胞活化增强,表现出焦虑样行为,激活VTA多巴胺能神经元改善了LPS处理小鼠的焦虑样行为。Objective:To observe the changes of anxiety-like behaviors in the lipopolysaccharide(LPS)-treated mice by activating dopaminergic neurons in the ventral dorsal tegmental area(VTA),to understand the role of dopaminergic neurons in VTA on anxiety-like behaviors in the LPS-treated mice.Methods:Adult male C57 mice were randomly divided into control group and LPS group.LPS group was injected intraperitoneally with 100μg/kg lipopolysaccharide.One day after,open field and elevated plus maze experiments were conducted to test the anxiety in mice.Were conducted to test the activities of neurons and astroytes in the VTA of mice.Adult male DAT-cre mice were randomly divided into LPS group and LPS+chemogenetic group.In LPS group,rAAV-DIO-mCherry virus was bilaterally injected into the VTA three weeks before LPS injection,while in the LPS+chemogenetic group,rAAV-DiO-hM3 Dq-mCherry virus was injected.One day after LPS injection,the mice in the two groups were intraperitoneal injected with clozapine N-oxide(CNO).Anxiety-like behaviors of the mice in the open field and elevated plus maze tests were observed after 30 minutes.Results:Compared with the control group,there was no significant difference in the total distance in LPS group(P>0.05),while the distance entered into the center zone in the LPS mice was decreased(P<0.05).During the evaluate plus maze test,the exploring time of LPS group spend in the open arm was significantly decreased(P<0.05).In the immunofluorescence experiment,the activation level of GFAP in the VTA region of LPS group mice was obvious increased,while the expression of the c-Fos positive neurons in VTA decreased than those in the control mice.The chemogenetic results showed that the distance in the center zone and the exploring time in the open arm of the LPS+chemogenetic group were significantly increased(P<0.05).Conclusion:Mice treated with LPS could induce the activation of astrocytes in the VTA and enhance the anxiety-like behavior.Activation of VTA-dopaminergic neurons can improve anxiety-like behav

关 键 词：脂多糖(LPS) 腹侧被盖区(VTA) 焦虑 多巴胺能神经元 小鼠 

分 类 号：R749.72[医药卫生—神经病学与精神病学]