摘要
本文旨在探讨在慢性应激性抑郁发生过程中海马神经肽Y(neuropeptide Y,NPY)和一氧化氮合酶(nitric oxide synthase,NOS)的关系。建立慢性不可预见性温和应激(chronic unpredictable mild stress,CUMS)抑郁模型,大鼠海马定位并分别微量注射NPY、NPY-Y1受体阻断剂GR231118和NOS抑制剂L-NAME,测量、计算动物体重变化并通过糖水偏爱测试、旷场和强迫游泳实验等方法检测大鼠行为,免疫组织化学方法检测海马内NPY、神经元型NOS(neuronal nitric oxide synthase,nNOS)和诱导型NOS(inducible nitric oxide synthase,iNOS)的表达。结果显示,与对照组相比,CUMS组大鼠表现出明显的抑郁样行为变化,且海马NPY表达下降、NOS表达显著升高;海马微量注射NPY明显改善应激引起的抑郁样行为表现,并降低海马NOS表达;用GR231118选择性阻断NPY-Y1受体后,大鼠的行为学表现能力下降,海马NOS表达升高;而CUMS以及GR231118所导致的行为学表现能力下降的现象均可被海马微量注射L-NAME所反转。以上结果表明,CUMS引起海马NPY表达下降,NOS表达升高,NO过量产生,导致抑郁发生;而NPY通过NPY-Y1受体抑制NOS的过量表达是NPY抗抑郁的一个重要途径。
Accumulating evidence indicates an important role of hippocampal dendrite atrophy in the development of depression, while neuropeptide Y （NPY） participates in hippocampal dendrite growth. The present study was aimed to investigate the relationship between NPY and nitric oxide synthase （NOS） in chronic unpredictable mild stress （CUMS）-induced depression. CUMS-induced depression model was established in Sprague-Dawley rats. Intrahippocampal microinjections of NPY, NPY-Y1 receptor antagonist GR231118 and non-specific NOS inhibitor N-nitro-L-arginine methyl ester （L-NAME） 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 expressions of NPY, neuronal nitric oxide synthase （nNOS） and inducible nitric oxide synthase （iNOS） in hippocampus were detected by immunohistochemistry. The results showed that, compared with the control group, rats receiving CUMS for 21 d or intrahippocampal microinjection of GR231118 showed a significant reduction in body weight and depression-like behavior, which included reductions in sucrose preference, locomotor activity, rearing and grooming in open field test, and increased duration of immobility in forced swimming test. Moreover, the expression of NPY significantly decreased （P0.01）, while the expressions of nNOS and iNOS increased obviously in the hippocampal dentate gyrus （DG） and CA3 regions （P0.01）. Intrahippocampal microinjections of NPY prevented the depression-like behavioral changes induced by CUMS and decreased the expressions of nNOS and iNOSin the hippocampal DG and CA3 regions （P0.01）. Intrahippocampal microinjections of GR231118 reduced behavioral ability of the rats dramatically and significantly increased the expressions of hippocampal nNOS and iNOS （P0.01）. Intrahippocampal microinjections of L-NAME suppressed the depression-like behavioral changes induced by CUMS or intrahippocampal microinjection of
出处
《生理学报》
CAS
CSCD
北大核心
2010年第3期237-246,共10页
Acta Physiologica Sinica
基金
supported by Fundamental Research Funds for the Central Universities(No.GK200901011)
Natural Science Foundation of Shaanxi Province
China(No.2006C240)
关键词
抑郁
海马
慢性不可预见性应激
神经肽Y
一氧化氮合酶
depression
hippocampus
chronic unpredictable mild stress
neuropeptide Y
nitric oxide synthase
