海马NMDA受体和NOS在慢性应激性抑郁发生中的作用及其相互关系  

Involvement of Hippocampal NMDA Receptor and Nitric Oxide Synthase in Depression Induced by Chronic Unpredicted Mild Stress

作　　者：李庆娇[1] 安书成[1] 

机构地区：[1]陕西师范大学生命科学学院,陕西西安710062

出　　处：《Zoological Research》2009年第6期653-661,共9页动物学研究（英文）

基　　金：陕西省自然科学基金资助项目(2006C240)

摘　　要：运用慢性不可预见性温和应激(chronic unpredicted mild stress,CUMS)建立抑郁动物模型,通过海马内微量注射、动物行为学观察及免疫组织化学方法检测海马内一氧化氮合酶(nitric oxide synthase,NOS)表达的变化,探讨CUMS诱发抑郁与海马谷氨酸N-甲基-D-天冬氨酸(N-methyl-D-aspartic acid,NMDA)受体和NOS的关系。结果发现:CUMS组大鼠表现出抑郁样行为变化,海马NOS表达显著升高;海马微量注射NMDA受体激动剂,动物行为学表现与CUMS组相同,NOS表达升高;海马微量注射非竞争性NMDA受体拮抗剂MK-801能明显改善应激引起的抑郁样行为表现,并降低海马NOS表达。这些结果表明慢性不可预见性应激可能使谷氨酸(glutamic acid,Glu)过量释放,NMDA受体过度激活,NOS高表达,NO过量产生,损伤海马神经元,导致抑郁发生。In order to investigate whether N-methyl-D-aspartic acid （NMDA） receptor and nitric oxide synthase （NOS） made contributions to the depression induced by chronic unpredicted mild stress （CUMS）, the depression model was established by using the CUMS. Using the stereotaxic and intra-hippocampal microinjection observing rat emotion and behaviors by the change in body weight, sucrose preference test, open field test and forced swimming test, and immunohistochemistry, and the expression of NOS in hippocampus were tested. The results showed that depression-like behavior and the expression of NOS increased in hippocampus induced by rats receiving CUMS for 21 days or intra-hippocampal injections of NMDA receptor agonist. Intra-hippocampal injection of noncompetitive NMDA receptor antagonist MK-801 significantly prevented CUMS-induced depression-like behavioral changes, and decreased the expression of NOS. These results provide evidence that CUMS resulting in development of depression may induce neurotoxicity in hippocampal neurons by stimulating Glu release, inducing excessive activation of NMDA receptor, and increasing expression of NOS.

关 键 词：抑郁 海马 NMDA受体 一氧化氮合酶 

分 类 号：Q42[生物学—神经生物学]