喹吡罗诱导的强迫症模型小鼠行为特征与神经机制研究  

Study on behavioral characteristics and neural mechanisms of obsessive-compulsive disorder model mouse induced by quinpirole

作　　者：邬建飞 蔡端芳 谭友果[1,2] 刘可智 陈元怀 王薏琳 刘宇 周勇 WU Jianfei;CAI Duanfang;TAN Youguo;LIU Kezhi;CHEN Yuanhuai;WANG Yilin;LIU Yu;ZHOU Yong(Zigong Mental Health Center,Zigong 643020,China;Zigong Institute of Brain Science,Zigong 643020,China)

机构地区：[1]自贡市精神卫生中心,四川自贡643020 [2]自贡市脑科学研究院,四川自贡643020

出　　处：《中国实验动物学报》2025年第3期342-352,共11页Acta Laboratorium Animalis Scientia Sinica

基　　金：国家重点研发项目(2022YFC2009900);自贡市科技计划项目(2023YKY11);自贡市卫生健康委员会科研课题(22yb001,24zd008);自贡市重点科技计划项目(2022-NKY-01-08,2023-NKY-02-13,2023-NKY-02-14);自贡市医学大数据与人工智能研究院协同创新类项目(2024-YGY-02-04)。

摘　　要：目的 探讨喹吡罗诱导的强迫症(obsessive-compulsive disorder, OCD)小鼠的行为学变化,再研究不同脑区神经元激活情况,并通过转录组测序技术检测差异表达基因(differentially expressed genes, DEGs)及富集的生物学通路,从而探讨OCD的发病机制。方法 将32只2月龄雄性C57BL/6J小鼠随机分为OCD组和对照组(n=16),OCD组小鼠间隔1 d颈部皮下注射喹吡罗(0.75 mg/kg),共19次,对照组小鼠注射生理盐水;造模完成后进行旷场测试、高架十字迷宫实验和大理石掩埋实验;行为学结束后取材,利用尼氏染色检测神经元损伤情况,利用免疫荧光染色检测c-Fos和Iba1蛋白的表达情况,利用转录组测序技术筛选DEGs和富集相关信号通路;利用Western Blot检测TNF-α、NF-κB p65、p-NF-κB p65和IL-6相关炎症因子的表达。结果 喹吡罗诱导的OCD小鼠表现出焦虑样行为和强迫样行为;海马区和下丘脑区神经元出现损伤情况;c-Fos和Iba1蛋白在皮层、纹状体和下丘脑等脑区的表达都增加;转录组测序结果OCD小鼠DEGs集于NF-κB信号通路;Western Blot结果显示TNF-α、p-NF-κB p65和IL-6等促炎症因子表达显著增加。结论 OCD小鼠多个脑区神经元被异常激活,小胶质细胞出现功能障碍,NF-κB信号通路激活引起的神经炎症伴随着OCD的发生过程。Objective Exploring the behavioral changes induced by quinpirole in obsessive-compulsive disorder(OCD) mouse, investigating the activation of neurons in different brain regions, and identifying differentially expressed genes(DEGs) and enriched biological pathways through transcriptome sequencing technology to elucidate the pathogenesis of OCD. Methods Randomly assign 32 male C57BL/6J mice, aged two months, to an OCD group and a control group(n = 16). Administering quinpirole(0.75 mg/kg) via subcutaneous injection to the OCD group mice every other day for a total of 19 injections, while the control group mice received an equivalent volume of saline solution. Following the completion of the model construction, open field testing, elevated plus maze testing, and marble burying tests were conducted. After the completion of behavioral studies, tissue samples were collected. Neuronal damage was assessed using Nissl staining, while the expression of c-Fos and Iba1 proteins was examined through immunofluorescence staining. Transcriptome sequencing technology was utilized to screen for differentially expressed genes and to enrich relevant signaling pathways. The expression of inflammatory cytokines, including TNF-α, NF-κB p65, phosphorylated NF-κB p65(p-NF-κB p65), and IL-6, was detected using Western Blot analysis. Results Mouse induced with OCD by quinpirole exhibit anxiety-like behaviors and compulsive-like behaviors. Neurons in the hippocampal and hypothalamic regions exhibit signs of damage. The expression of c-Fos and Iba1 proteins is increased in the cortex, striatum, hypothalamus, and other brain regions. Western Blot result indicate a significant increase in the expression of pro-inflammatory cytokines such as TNF-α, p-NF-κB p65, and IL-6. Conclusions In OCD mouse, neurons in multiple brain regions are abnormally activated, microglia exhibit dysfunction, and neuroinflammation induced by the activation of the NF-κB signaling pathway accompanies the development of OCD.

关 键 词：强迫症 转录制测序 神经炎症 NF-ΚB TNF-Α 小鼠 

分 类 号：Q95-33[生物学—动物学]