摘要
目的探究游泳运动和氟西汀对CUMS小鼠抑郁行为及GSK3β/β-catenin信号通路的影响。方法采用雄性C57BL/6小鼠,随机分为5组,每组8只:Con组,即普通控制组;CUMS组,实验小鼠接受7周的慢性不可预见性温和应激;CUMS+Saline组,从应激的第4周开始腹腔注射生理盐水4周;CUMS+Flu组,从应激的第4周开始腹腔注射抗抑郁药物氟西汀(Fluoxetine,Flu)4周;CUMS+Swim组,从应激的第4周开始进行游泳训练4周。实验干预结束后,所有小鼠接受行为学检测。断头处死取海马组织,采用Western blotting技术检测相关基因的蛋白表达水平。结果 (1)行为学实验显示,与Con组相比,CUMS组糖水偏好显著降低(P<0.05),强迫游泳(FST)和悬尾实验(TST)不动时间显著增加(P<0.01),开场实验(OFT)探洞次数显著减少(P<0.05);与CUMS+Saline组相比,CUMS+Flu组糖水偏好显著增加(P<0.05),FST和TST不动时间显著减少(P<0.05),OFT探洞次数显著增加(P<0.01);与CUMS组相比,CUMS+Swim组糖水偏好无显著变化,FST(P<0.05)和TST(P<0.01)不动时间显著减少,OFT探洞次数显著增加(P<0.01)。(2)Western blotting实验显示,与Con相比,CUMS组海马组织中pGSK3β(Ser9)、β-catenin的蛋白水平显著降低(P<0.05);与CUMS+Saline相比,CUMS+Flu组海马组织中β-catenin的蛋白水平显著升高(P<0.05),GSK3β、pGSK3β(Ser9)、pGSK3β(Tyr216)的蛋白水平无显著变化;与CUMS组相比,CUMS+Swim组海马组织中GSK3β(P<0.01)、pGSK3β(Ser9,P<0.05)、β-catenin(P<0.05)的蛋白水平显著升高。结论运动和氟西汀均可缓解CUMS所致的小鼠抑郁行为;慢性应激诱导抑郁行为可能涉及GSK3β/β-catenin信号通路的功能紊乱;运动和氟西汀均提高小鼠对慢性应激的耐受性从而控制抑郁病理进程,二者发挥作用的分子机制有所不同,运动缓解抑郁行为可能涉及纠正海马组织中GSK3β/β-catenin信号通路紊乱,而氟西汀缓解抑郁行为可能是非GSK3β/β-catenin依赖性的。研究论证了慢性应�
Objective The current study aims to explore the mechanism of exercise and fluoxetine in the treatment of depression.Methods A total of 50 male C57/BL6 mice,were randomly divided into five groups:Con,Control;CUMS,The experimental mice experienced 7 weeks of chronic unpredictable mild stress;CUMS+Saline,fourth weeks of CUMS began to inject saline;CUMS+Flu,fourth weeks of CUMS began to inject fluoxetine;CUMS+Swim,fourth weeks of CUMS began to swimming exercise.After 7 weeks of experimental treatment,behavioral tests were performed.Mice were decapitated;the hippocampus was rapidly and carefully extracted.Western blotting were used to examine the protein levels of GSK3β,pGSK3β(Ser9),pGSK3β(Tyr216),andβ-catenin.Results(1)CUMS exposure induced depression-like behaviors,including reduced sucrose preference(P<0.05),increased immobility time in FST and TST(P<0.01),reduced poking number in OFT(P<0.05),compared to the control.Fluoxetine could ameliorates depression-like behaviors induced by CUMS,including increased sucrose preference(P<0.05),decreased immobility time in FST and TST(P<0.05),increased poking number in OFT(P<0.01),compared to the CUMS+Saline group.Swimming exercise could ameliorates depression-like behaviors induced by CUMS,including decreased immobility time in FST(P<0.05)and TST(P<0.01),increased poking number in OFT(P<0.01),compared to the CUMS group.(2)CUMS exposure significantly decreased the protein levels of pGSK3β(Ser9),andβ-catenin in HPC(P<0.05),compared to the control.Fluoxetine significantly increased the protein level ofβ-catenin in HPC(P<0.05),compared to the CUMS+Saline group.Swimming exercise significantly increased the protein level of GSK3β(P<0.01),pGSK3β(Ser9,P<0.05),andβ-catenin(P<0.05)in HPC,compared to the CUMS group.Conclusion Fluoxetine and exercise can enhance the tolerance of CUMS exposure and control the pathological process of depression.Stress-induced depression is associated with the dysfunction of GSK3β/β-catenin signaling pathway,and exercise ameliorated depression-li
作者
夏杰
刘微娜
漆正堂
XIA Jie;LIU Weina;QI Zhengtang(The Key Laboratory of Adolescent Health Assessment and Exercise Intervention,East China Normal University,Shanghai 200241,China;School of Physical Education&Health Care,East China Normal University,Shanghai 200241,China)
出处
《西安体育学院学报》
CSSCI
北大核心
2019年第5期610-618,630,共10页
Journal of Xi'an Physical Education University
基金
国家自然科学基金项目(31871208)
上海市自然科学基金项目(18ZR1412000)
