海马miR-182在慢性应激抑郁模型大鼠中的变化  

HIPPOCAMPAL MIR- 182 REGULATES DEPRESSIVE- LIKE BEHAVIOR INDUCED BY CHRONIC STRESS IN RATS

作　　者：温晨光[1] 王慎军[1] 张若曦[1] 朱维莉[1] 陆林[1] 

机构地区：[1]北京大学中国药物依赖性研究所,北京100191

出　　处：《中国药物依赖性杂志》2015年第5期345-350,共6页Chinese Journal of Drug Dependence

基　　金：国家自然科学基金(81371489);北京高等学校青年英才计划项目(YETP0068)

摘　　要：目的:探索miRNA与抑郁症的关系,为揭示应激诱导的抑郁症发生机制和开发新型抗抑郁症药物奠定基础。方法:建立慢性不可预见性轻度应激(Chronic unpredictable mild stress,CUMS)抑郁症动物模型,运用miRNA二代测序、miRNA差异表达分析、荧光定量PCR(q PCR)等方法检测抑郁模型动物miRNA表达谱的变化。结果:(1)大鼠经历5周连续的不可预见性应激,通过检测糖水偏好、体重增加、自发活动减少等指标表明大鼠形成抑郁样行为。利用Solexa测序技术对大鼠海马miRNA表达谱进行分析,结果发现与对照组比较,抑郁模型组变化幅度超过两倍的miRNAs有:miR-1224上调,miR-1249、miR-182、miR-183、miR-204下调。(2)对于差异表达的miRNA进行靶基因分析发现,miR-182所调控的脑源性营养因子(brain derived neurotrophic factor,BDNF)、CLOCK、胰岛素样生长因子1型受体(insulin-like growth factor 1 receptor,IGF1R)、cAMP反应元件结合蛋白1(c AMP-response element binding protein 1,CREB1)与抑郁症的病因具有密切的联系。用定量PCR对慢性应激模型大鼠和对照组大鼠海马三个亚区miR-182的表达量进行分析发现,海马齿状回(dentate gyrus,DG)miR-182下调程度最为显著。CA1(cornuammonis 1)区和CA3(cornuammonis 3)区miR-182出现下调倾向,但无统计学差异。结论:大鼠海马DG区miR-182可能参与调控了慢性应激所致大鼠抑郁样行为的形成。Objective：To determine the relationship between the miRNA and depression induced by stress,and provide the evidence for the development of new type of antidepressant treatment.Methods：Chronic unpredictable mild stress（CUMS）,sucrose preference test,miRNA expression profiling,quantitive PCR（qPCR）,bioinformatics and behavioral tests were used.Results：A miRNA（miR- 1224） was significantly increased,and four miRNAs were found to be significantly decreased（miR- 1249,182,183,204）.The results of qPCR indicated that the level of miR- 182 expression in dentate gyrus（DG） of CUMS group is much lower than that of the control group.The levels of miR- 182 of model group decreased in hippocampal CA1 and CA3 areas,but there were no significant differences when compared with control group.Conclusion：miR- 182 may be an important molecular regulator that controls the pathophysiologic process of chronic stress in the hippocampus and the neuroadaptations associated with depression.

关 键 词：抑郁症 应激 海马 MIRNA 表达谱 

分 类 号：R749[医药卫生—神经病学与精神病学]