Katzav Aviva, Solodeev Inna, Brodsky Ori, Chapman Joab, Pick Chaim G, Blank Miri, Zhang Wei, Reichlin Morris, Shoenfeld Yehuda
Tel Aviv University, Tel Aviv, Israel, and Sheba Medical Center, Tel Hashomer, Israel.
Arthritis Rheum. 2007 Mar;56(3):938-48. doi: 10.1002/art.22419.
Autoantibodies against ribosomal P proteins are linked to the neuropsychiatric manifestations of systemic lupus erythematosus (SLE). The present study was undertaken to assess how the specific brain-binding autoantibody anti-ribosomal P can induce a depression-type psychiatric disorder in mice.
Mice were injected intracerebroventricularly with affinity-purified human anti-ribosomal P antibodies or IgG as control. Pharmacologic and immunologic treatments included the antidepressant drug fluoxetine, the antipsychotic drug haloperidol, and antiidiotypic antibodies. Behavior was assessed by the forced swimming test, motor deficits by rotarod, grip strength, and staircase tests, and cognitive deficits by T-maze alternation and passive avoidance tests.
Anti-ribosomal P antibodies induced depression-like behavior in the mice (mean +/- SEM 147.3 +/- 19.2 seconds of immobility versus 75.2 +/- 12.1 seconds of immobility in IgG-injected control mice; P < 0.005). The anti-ribosomal P antibody-induced depression-like behavior was partially blocked by a specific antiidiotypic antibody and significantly blocked by long-term treatment with fluoxetine, but not by short- or long-term treatment with haloperidol. The depressive behavior was not associated with any motor or cognitive deficits. Anti-ribosomal P antibodies specifically stained neurons in the hippocampus, cingulate cortex, and the primary olfactory piriform cortex, compatible with the previously described binding to the membrane-bound P0 ribosomal protein.
This is the first report of an experimental depression induced by a specific autoantibody. The results implicate olfactory and limbic areas in the pathogenesis of depression in general, and in central nervous system dysfunction in SLE in particular.
针对核糖体P蛋白的自身抗体与系统性红斑狼疮（SLE）的神经精神表现相关。本研究旨在评估特异性脑结合自身抗体抗核糖体P如何在小鼠中诱发抑郁型精神障碍。
给小鼠脑室内注射亲和纯化的人抗核糖体P抗体或作为对照的IgG。药理和免疫治疗包括抗抑郁药氟西汀、抗精神病药氟哌啶醇和抗独特型抗体。通过强迫游泳试验评估行为，通过转棒试验、握力试验和阶梯试验评估运动缺陷，通过T迷宫交替试验和被动回避试验评估认知缺陷。
抗核糖体P抗体在小鼠中诱发了抑郁样行为（平均±标准误，不动时间为147.3±19.2秒，而注射IgG的对照小鼠为75.2±12.1秒；P<0.005）。抗核糖体P抗体诱发的抑郁样行为被特异性抗独特型抗体部分阻断，被氟西汀长期治疗显著阻断，但未被氟哌啶醇短期或长期治疗阻断。抑郁行为与任何运动或认知缺陷均无关。抗核糖体P抗体特异性地标记海马体、扣带回皮质和初级嗅觉梨状皮质中的神经元，这与先前描述的与膜结合的P0核糖体蛋白的结合情况相符。
这是关于由特异性自身抗体诱发实验性抑郁的首次报道。结果表明，嗅觉和边缘系统区域总体上参与了抑郁的发病机制，特别是在SLE的中枢神经系统功能障碍中。
