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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

余伶, 安书成^*, 廉婷

陕西师范大学生命科学学院，西安 710062

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。

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：Q189；R749.4

[Involvement of hippocampal NMDA receptor and neuropeptide Y in depression induced by chronic unpredictable mild stress.] [Ariticle in Chinese]

YU Ling, AN Shu-Cheng^*, LIAN Ting

College of Life Science, Shaanxi Normal University, Xi'an 710062, China

Abstract

The present study was aimed to investigate the role and relationship between N-methyl-D-aspartic acid (NMDA) receptorand neuropeptide Y (NPY) in depression induced by chronic unpredictable mild stress (CUMS). CUMS-induced depression modelwas established in Sprague-Dawley rats. Intrahippocampal injections of NMDA, non-competitive NMDA receptor antagonist MK-801 and NPY-Y1 receptor antagonist GR231118 were respectively adopted by rat brain stereotaxic coordinates. The behavioralobservations were conducted by sucrose consumption test, open field test and forced swimming test. The expression of NPY inhippocampus was detected by immunohistochemistry. The results showed that compared with the control group, rats receivingCUMS for 21 days or intrahippocampal injection of GR231118 or NMDA showed depression-like behavioral changes, including areduction in sucrose preference, body weight, locomotor activity, rearing and grooming in open field test, and increased duration ofimmobility in forced swimming test. Intrahippocampal injection of NMDA decreased the expression of NPY in hippocampal CA3region and dentate gyrus (DG) region. Intrahippocampal injection of MK-801 improved the depression-like behavioral changes inducedby CUMS, and increased the expression of NPY in hippocampal CA3 region and DG region. Co-injection of GR231118 and MK-801showed that GR231118 suppressed the antidepressant effect of MK-801. These data suggest that CUMS might induce depressionthrough excessive release of glutamate (Glu), over-activation of NMDA receptors, and downregulation of NPY. Antidepressant effectof NPY was mainly mediated via NPY-Y1 receptor.

Key words: chronic unpredictable mild stress; depression; hippocampus; N-methyl-D-aspartic acid receptor; neuropeptide Y

收稿日期：2009-11-12　　录用日期：2010-01-11

通讯作者：安书成　　E-mail: shuchengan@snnu.edu.cn

引用本文：

余伶, 安书成, 廉婷. 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[J]. 生理学报 2010; 62 (1): 14-22.

YU Ling, AN Shu-Cheng, LIAN Ting. [Involvement of hippocampal NMDA receptor and neuropeptide Y in depression induced by chronic unpredictable mild stress.] [Ariticle in Chinese] . Acta Physiol Sin 2010; 62 (1): 14-22 (in Chinese with English abstract).