海马NMDA受体与神经肽Y在慢性应激性抑郁发生中的作用及其关系  

Involvement of hippocampal NMDA receptor and neuropeptide Y in depression induced by chronic unpredictable mild stress

作　　者：余伶[1] 安书成[1] 廉婷[1] 

机构地区：[1]陕西师范大学生命科学学院,西安710062

出　　处：《生理学报》2010年第1期14-22,共9页Acta Physiologica Sinica

基　　金：supported by the Natural Science Foundation of Shaanxi Province;China(No.2006C_240)

摘　　要：本文旨在探讨N-甲基-D-天冬氨酸(N-methyl-D-aspartic acid,NMDA)受体与神经肽Y(neuropeptide Y,NPY)在慢性应激抑郁发生中的作用与关系。建立慢性不可预见性温和应激(chronic unpredictable mild stress,CUMS)抑郁模型,海马单侧分别微量注射非竞争性NMDA受体拮抗剂MK-801、NPY-Y1受体阻断剂GR231118和NMDA后,利用体重测量及糖水偏爱测试、强迫游泳及敞箱实验等方法观察动物行为变化,运用免疫组织化学方法检测海马CA3区和齿状回(dentate gyrus,DG)内NPY的表达。结果显示,CUMS组大鼠表现出抑郁样行为变化,海马NPY表达显著降低;海马微量注射NMDA或NPY-Y1受体阻断剂GR231118,动物行为学表现均与CUMS组相同,注射NMDA可使NPY表达显著降低;海马微量注射MK-801能明显改善应激引起的抑郁样行为表现,并使海马NPY表达增加。联合注射GR231118与MK-801后,GR231118可以显著减弱MK-801的抗抑郁样行为的效应。以上结果表明,CUMS可能使谷氨酸(glutamic acid,Glu)过量释放,NMDA受体过度激活,抑制NPY表达,导致抑郁发生。NPY抗抑郁作用主要是通过NPY-Y1受体实现。The present study was aimed to investigate the role and relationship between N-methyl-D-aspartic acid （NMDA） receptor and neuropeptide Y （NPY） in depression induced by chronic unpredictable mild stress （CUMS）.CUMS-induced depression model was established in Sprague-Dawley rats.Intrahippocampal injections of NMDA,non-competitive NMDA receptor antagonist MK801 and NPY-Y1 receptor antagonist GR231118 were respectively adopted by rat brain stereotaxic coordinates.The behavioral observations were conducted by sucrose consumption test,open field test and forced swimming test.The expression of NPY in hippocampus was detected by immunohistochemistry.The results showed that compared with the control group,rats receiving CUMS for 21 days or intrahippocampal injection of GR231118 or NMDA showed depression-like behavioral changes,including a reduction in sucrose preference,body weight,locomotor activity,rearing and grooming in open field test,and increased duration of immobility in forced swimming test.Intrahippocampal injection of NMDA decreased the expression of NPY in hippocampal CA3 region and dentate gyrus （DG） region.Intrahippocampal injection of MK-801 improved the depression-like behavioral changes induced by CUMS,and increased the expression of NPY in hippocampal CA3 region and DG region.Co-injection of GR231118 and MK801showed that GR231118 suppressed the antidepressant effect of MK-801.These data suggest that CUMS might induce depression through excessive release of glutamate （Glu）,over-activation of NMDA receptors,and downregulation of NPY.Antidepressant effect of NPY was mainly mediated via NPY-Y1 receptor.

关 键 词：慢性不可预见性温和应激 抑郁 海马 NMDA受体 神经肽Y 

分 类 号：R749.4[医药卫生—神经病学与精神病学]