P2X7受体介导慢性应激诱导的小鼠抑郁样行为  

P2X7 receptor mediates chronic stress-induced depressive-like behaviors in mice

作　　者：刘青青 曹珍 卞理 LIU Qingqing;CAO Zhen;BIAN Li(Department of Pharmacy,the Third Affiliated Hospital of Nantong University,the Third People′s Hospital of Nantong Nantong,Jiangsu 226000,China)

机构地区：[1]南通大学附属南通第三医院,南通市第三人民医院药学部,江苏南通226000

出　　处：《徐州医科大学学报》2024年第10期703-711,共9页Journal of Xuzhou Medical University

基　　金：南通市卫生健康委员会青年科研基金项目(WQ2016018)。

摘　　要：目的探索嘌呤能离子通道型受体7(P2X7R)参与抑郁症的病理机制,为抑郁症的治疗提供新的治疗靶点。方法采用慢性社会挫败应激(CSDS)建立小鼠抑郁模型,悬尾实验、强迫游泳实验、糖水偏好实验和社会互动实验检测小鼠行为学变化。蛋白质印迹法检测脑源性神经营养因子(BDNF)和酪氨酸激酶受体B(TrkB)蛋白表达水平,免疫荧光法检测各组小鼠海马神经发生情况。结果与对照组相比,CSDS组小鼠不动时间明显增加(P<0.01)、而糖水偏好指数、社会互动时间、BDNF/TrkB蛋白表达水平以及双皮质素(DCX)阳性细胞数目明显降低(P<0.01);与CSDS组相比,CSDS+A438079组小鼠不动时间显著减少(P<0.01)、而糖水偏好指数、社会互动时间、BDNF/TrkB蛋白表达水平以及DCX阳性细胞数目显著增加(P<0.01)。结论P2X7R拮抗剂(A438079)通过激活BDNF/TrkB信号通路减轻CSDS诱导的小鼠抑郁样行为,这些发现为抑郁症的防治提供了新的治疗靶点。Objective To explore the role of purinergic ion channel receptor 7(P2X7R)in the pathological mecha-nism of depression and provide novel theraputic targets for depression treatment.Methods A mouse model of depression was established through chronic social defeat stress(CSDS).Behavioral changes were assessed using the tail suspension test,forced swim test,sucrose preference test,and social interaction test.The levels of brain-derived neurotrophic factor(BDNF)and tyrosine kinase receptor B(TrkB)were detected by Western blot.The hippocampal neurogenesis was ex-amined by immunofluorescence in each group of mice.Results Compared with the control group,mice in the CSDS group showed a significant increase in immobility time(P<0.01),while sucrose preference index,social interaction time,BDNF/TrkB protein levels,and the number of doublecortin(DCX)-positive cells remarkably decreased(P<0.01).Compared with the CSDS group,mice in the CSDS+A438079 group exhibited a significant decrease in immobility time(P<0.01),while sucrose preference index,social interaction time,BDNF/TrkB protein levels,and the number of DCX-positive cells remarkably increased(P<0.01).Conclusions The P2X7R antagonist(A438079)alleviates CSDS-induced depression-like behaviors in mice by activating the BDNF/TrkB signaling pathway.These findings provide new therapeutic targets for the prevention and treatment of depression.

关 键 词：抑郁症 嘌呤能离子通道型受体7 慢性社会挫败应激 酪氨酸激酶受体B 神经发生 

分 类 号：R749.4[医药卫生—神经病学与精神病学]