β-arrestin-1 levels:: Reduced in leukocytes of patients with depression and elevated by antidepressants in rat brain
β-arrestin-1 levels:: Reduced in leukocytes of patients with depression and elevated by antidepressants in rat brain
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DOI：
10.1176/appi.ajp.161.11.2066
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发表时间：
2004-11-01
影响因子：
17.7
通讯作者：
Schreiber, G
中科院分区：
文献类型：
--
作者：
Avissar, S;Matuzany-Ruban, A;Schreiber, G
目的：β-Arrestins在G蛋白偶联受体脱敏中发挥重要作用。β-抑制蛋白干扰G蛋白受体相互作用，从而导致G蛋白介导的受体信号传导脱敏。G蛋白受体信号传导及其脱敏以前被牵连在情绪障碍的病理生理学和抗抑郁药和情绪稳定治疗的作用机制。本研究的目的是在定量评估β-arrestin-1水平在白细胞中的抑郁症患者和抗抑郁药对β-arrestin-1水平在大鼠brain.Method：β-arrestin-1测量进行了皮质，海马和纹状体的大脑区域的大鼠慢性intragastrically治疗丙咪嗪，地昔帕明，或氟伏沙明。在36名未经治疗的重度抑郁症患者和32名健康志愿者的单核白细胞中进行了类似的测量。结果：3种抗抑郁药均能显著升高大鼠皮层和海马中β-Arrestin-1的表达，而纹状体中β-Arrestin-1的表达无明显变化。这个过程在10天内变得显著，并需要2-3周才能达到最大增加。抑郁症患者的单核细胞白细胞β-arrestin-1的免疫反应量显着减少。β-arrestin-1水平的减少显着相关的抑郁symptoms.Conclusions的严重程度：在大鼠的研究结果表明β-arrestin-1海拔作为抗抑郁药诱导的受体下调的生化机制。在人类受试者中的发现支持β-arrestin-1在情绪障碍的病理生理学中的意义。抑郁症患者的β-Arrestin-1测量可能作为抑郁症的生化标志物。
Objective: beta-Arrestins play a pivotal role in G protein-coupled receptor desensitization. beta-Arrestins interfere in G protein receptor interaction, thus leading to desensitization of G protein-mediated receptor signaling. G protein receptor signaling and its desensitization were previously implicated in the pathophysiology of mood disorders and in the mechanism of action of antidepressant and mood-stabilizing treatments. The present study aims at quantitatively evaluating beta-arrestin-1 levels in leukocytes of patients with major depression and the effect of antidepressants on beta-arrestin-1 levels in rat brain.Method: beta-arrestin-1 measurements were carried out in cortical, hippocampal, and striatal brain regions of rats chronically intragastrically treated with either imipramine, desipramine, or fluvoxamine. Similar measurements were conducted in mononuclear leukocytes of 36 untreated patients with major depression and 32 healthy volunteer subjects. beta-Arrestin-1 levels were evaluated through immuno-blot analyses using monoclonal antibodies to beta-arrestin-1.Results: beta-Arrestin-1 levels were significantly elevated by all three antidepressants in rat cortex and hippocampus, while in the striatum no alterations could be detected. This process became significant within 10 days and took 2-3 weeks to reach maximal increase. Mononuclear leukocytes of patients with depression showed significantly reduced immunoreactive quantities of beta-arrestin-1. The reduction in beta-arrestin-1 levels was significantly correlated with the severity of depressive symptoms.Conclusions: The findings in the rat study suggest beta-arrestin-1 elevation as a biochemical mechanism for antidepressant-induced receptor down-regulation. The findings in human subjects support the implication of beta-arrestin-1 in the pathophysiology of mood disorders. beta-Arrestin-1 measurements in patients with depression may potentially serve as a biochemical marker for depression.