Mesquita Ana Raquel, Correia-Neves Margarida, Roque Susana, Castro António Gil, Vieira Paulo, Pedrosa Jorge, Palha Joana Almeida, Sousa Nuno
Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal.
J Psychiatr Res. 2008 Dec;43(2):89-97. doi: 10.1016/j.jpsychires.2008.02.004. Epub 2008 Apr 18.
The role of pro-inflammatory cytokines in psychiatric disorders has been the focus of great research attention in recent years. Paradoxically, the same is not true for anti-inflammatory cytokines. In the present study, we assessed the behavioral profile of animals with altered expression of the anti-inflammatory cytokine IL-10. We performed a battery of tests to assess anxiety, depressive-like and cognitive behaviors in mice overexpressing IL-10 (PMT10) and IL-10(-/-) animals; in the later mice we also tested the behavioral effect of IL-10 administration. In the forced-swimming test, IL-10(-/-) females displayed increased depressive-like behavior; importantly, this phenotype was reverted by the injection of IL-10. Moreover, mice overexpressing IL-10 presented a decreased depressive-like behavior. Despite the presence of a similar trend, male animals did not reach significant differences in depressive-like behavior. Assessment in the open-field showed that the absence of IL-10 decreased the percentage of time spent in the center of the arena in both male and female mice, while male animals overexpressing IL-10 revealed an opposite behavior. For both sexes, imbalance in IL-10 levels did not affect spatial reference memory. In conclusion, variations in IL-10 expression are associated with an altered depressive-like behavior, but do not influence cognitive performance. Interestingly, IL-10 imbalance produced more profound behavioral changes in females than in male animals. This is in accordance with clinical data demonstrating an increased susceptibility of women to mood disorders, suggesting an interplay between anti-inflammatory cytokines and sexual steroids.
近年来，促炎细胞因子在精神疾病中的作用一直是大量研究关注的焦点。矛盾的是，抗炎细胞因子的情况并非如此。在本研究中，我们评估了抗炎细胞因子白细胞介素-10（IL-10）表达改变的动物的行为特征。我们进行了一系列测试，以评估过表达IL-10的小鼠（PMT10）和IL-10基因敲除（IL-10(-/-)）小鼠的焦虑、抑郁样和认知行为；在后者中，我们还测试了注射IL-10的行为效果。在强迫游泳试验中，IL-10(-/-)雌性小鼠表现出增加的抑郁样行为；重要的是，这种表型通过注射IL-10得以逆转。此外，过表达IL-10的小鼠表现出减少的抑郁样行为。尽管存在类似趋势，但雄性动物在抑郁样行为方面没有达到显著差异。旷场试验评估表明，缺乏IL-10会降低雄性和雌性小鼠在旷场中央停留的时间百分比，而过表达IL-10的雄性动物则表现出相反的行为。对于两性而言，IL-10水平的失衡并不影响空间参考记忆。总之，IL-10表达的变化与抑郁样行为的改变有关，但不影响认知表现。有趣的是，IL-10失衡在雌性动物中产生的行为变化比雄性动物更显著。这与临床数据一致，临床数据表明女性对情绪障碍的易感性增加，提示抗炎细胞因子与性类固醇之间存在相互作用。
