Chronic unpredictable mild stress-induced depressive-like behavior and dysregulation of brain levels of biogenic amines in Drosophila melanogaster
Chronic unpredictable mild stress-induced depressive-like behavior and dysregulation of brain levels of biogenic amines in Drosophila melanogaster
复制标题
DOI：
10.1016/j.bbr.2018.05.016
复制
发表时间：
2018-10-01
影响因子：
2.7
通讯作者：
Prigol, Marina
中科院分区：
文献类型：
--
作者：
Araujo, Stifani Machado;Poetini, Marcia Rosula;Prigol, Marina
抑郁症的发病机制可能涉及反复暴露于几个不可预测的压力源。本研究旨在探讨慢性不可预测的轻度应激（CIMTS）引起的变化，并评估预测抑郁样行为的行为和神经化学变化。雄性黑腹果蝇以不可预测和慢性的方式暴露于具有几种应激源（冷、热、饥饿和睡眠剥夺）的COMS中10天。在处理结束时，进行体内行为测试（旷场、攻击、强迫游泳、交配、明/暗箱、雄性生育力评价、蔗糖偏好、体重评价）和离体分析（多巴胺和5-羟色胺水平）。使用这个模型，我们获得了有助于在果蝇中构建抑郁模型的结果，在该模型中，我们再现了与抑郁症状相对应的一些行为表型，例如强迫游泳测试中的不动性，光/暗测试中的探索减少，交配行为的变化，攻击性测试中的变化，蔗糖偏好降低和体重减轻，此外，与对照组相比，血清素和多巴胺的水平显著降低。在我们的研究中，氟西汀被用作阳性对照，以证明果蝇中由抗抑郁药诱导的抑郁样行为可以被逆转。总之，雄性果蝇暴露于COMS显示抑郁样表型，虽然这构成了一些限制作为抑郁症的动物模型，它符合一些标准要求是一个有效的模型，如良好的面子和结构效度。
The etiopathogenesis of depression may involve repeated exposure to several unpredictable stressors. This study was conducted to investigate changes induced by chronic unpredictable mild stress (CUMS) and to assess behavioral and neurochemical changes that predict depressive-like behavior in Drosophila melanogaster. Male Drosophila melanogaster flies were exposed to CUMS with several stressors (cold, heat, starvation, and sleep deprivation) in an unpredictable and chronic manner for ten days. At the end of treatment, in vivo behavioral tests (open field, aggression, forced swimming, mating, light/dark box, male fertility evaluation, sucrose preference, weight evaluation) and ex vivo analyses (dopamine and serotonin levels) were performed. Using this CUMS model, we obtained results that contribute to the construction of a depressive model in Drosophila, where we reproduce some behavioral phenotypes corresponding to depressive symptoms, such as immobility in the forced swimming test, less exploration in the light/dark test, changes in mating behavior, changes in the aggressiveness test, reduced sucrose preference, and weight-loss, in addition to a significant reduction in the levels of serotonin and dopamine when compared to the control group. Fluoxetine was used in our study as a positive control to demonstrate that CUMS-induced depressive-like behaviors in flies can be reversed by antidepressants. In conclusion, male Drosophila melanogaster exposed to CUMS display a depressive-like phenotype, and, while this poses some limitations as an animal model for depression, it meets some of the criteria required to be a valid model, such as good face and construct validity.