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Experimental Social Stress: Dopaminergic Receptors, Oxidative Stress, and c-Fos Protein Are Involved in Highly Aggressive Behavior.
Frontiers in Cellular Neuroscience ( IF 5.3 ) Pub Date : 2021-08-17 , DOI: 10.3389/fncel.2021.696834
Renata M Felippe 1 , Gabriel M Oliveira 2 , Rafaela S Barbosa 1 , Betina D Esteves 1 , Beatriz M S Gonzaga 1 , Samuel I M Horita 1, 3 , Luciana R Garzoni 1 , Daniela G Beghini 1 , Tânia C Araújo-Jorge 1 , Viviane M S Fragoso 1
Affiliation  

Aggression is defined as hostile behavior that results in psychological damage, injury and even death among individuals. When aggression presents itself in an exacerbated and constant way, it can be considered escalating or pathological. The association between social stress and the emergence of exacerbated aggressiveness is common and is suggested to be interconnected through very complex neurobiological factors. For example, alterations in the expression of the dopaminergic receptors D1 and D2, reactive oxygen species (ROS) and the c-Fos protein in the cortex have been observed. Our objective was to analyze which factors are involved at the neurobiological level in the highly aggressive response of Swiss Webster adult male mice in a vivarium. In this work, we investigated the relationship among dopaminergic receptors, the production of ROS and the expression of c-Fos. Mice with exacerbated aggression were identified by the model of spontaneous aggression (MSA) based on the grouping of young mice and the regrouping of the same animals in adulthood. During the regrouping, we observed different categories of behavior resulting from social stress, such as (i) highly aggressive animals, (ii) defeated animals, and (iii) harmonic groups. To evaluate the dopaminergic system and the c-Fos protein, we quantified the expression of D1 and D2 dopaminergic receptors by Western blotting and fluorescence immunohistochemistry and that of the c-Fos protein by fluorescence immunohistochemistry. The possible production of ROS was also evaluated through the dihydroethidium (DHE) assay. The results showed that aggressive and subordinate mice showed a reduction in the expression of the D1 receptor, and no significant difference in the expression of the D2 receptor was observed between the groups. In addition, aggressive mice exhibited increased production of ROS and c-Fos protein. Based on our results, we suggest that exacerbated aggression is associated with social stress, dysregulation of the dopaminergic system and exacerbated ROS production, which leads to a state of cellular oxidative stress. The overexpression of c-Fos due to social stress suggests an attempt by the cell to produce antioxidant agents to reduce the toxic cellular concentration of ROS.

中文翻译:

实验性社会压力:多巴胺能受体、氧化应激和 c-Fos 蛋白与高度攻击性行为有关。

侵略被定义为导致个人心理伤害、伤害甚至死亡的敌对行为。当攻击性以加剧和持续的方式出现时,它可以被认为是升级或病态的。社会压力与攻击性加剧之间的关联很常见,并且被认为通过非常复杂的神经生物学因素相互关联。例如,已经观察到皮质中多巴胺能受体 D1 和 D2、活性氧 (ROS) 和 c-Fos 蛋白表达的改变。我们的目标是分析哪些因素在神经生物学水平上与瑞士韦伯斯特成年雄性小鼠在动物饲养场中的高度攻击性反应有关。在这项工作中,我们研究了多巴胺能受体之间的关系,ROS 的产生和 c-Fos 的表达。基于年轻小鼠的分组和成年后相同动物的重新分组,通过自发性攻击 (MSA) 模型识别具有加剧攻击性的小鼠。在重组过程中,我们观察到由社会压力引起的不同类别的行为,例如 (i) 高度攻击性的动物,(ii) 被打败的动物,以及 (iii) 和谐群体。为了评估多巴胺能系统和 c-Fos 蛋白,我们通过蛋白质印迹和荧光免疫组织化学量化了 D1 和 D2 多巴胺能受体的表达,并通过荧光免疫组织化学量化了 c-Fos 蛋白的表达。还通过二氢乙锭 (DHE) 测定评估了 ROS 的可能产生。结果显示,攻击性和下属小鼠的 D1 受体表达减少,组间 D2 受体表达没有显着差异。此外,攻击性小鼠表现出增加的 ROS 和 c-Fos 蛋白的产生。根据我们的研究结果,我们认为加剧的攻击性与社会压力、多巴胺能系统失调和 ROS 产生加剧有关,这会导致细胞氧化应激状态。由于社会压力导致 c-Fos 的过度表达表明细胞试图产生抗氧化剂以降低 ROS 的毒性细胞浓度。攻击性小鼠表现出增加的 ROS 和 c-Fos 蛋白的产生。根据我们的研究结果,我们认为加剧的攻击性与社会压力、多巴胺能系统失调和 ROS 产生加剧有关,这会导致细胞氧化应激状态。由于社会压力导致 c-Fos 的过度表达表明细胞试图产生抗氧化剂以降低 ROS 的毒性细胞浓度。攻击性小鼠表现出增加的 ROS 和 c-Fos 蛋白的产生。根据我们的研究结果,我们认为加剧的攻击性与社会压力、多巴胺能系统失调和 ROS 产生加剧有关,这会导致细胞氧化应激状态。由于社会压力导致 c-Fos 的过度表达表明细胞试图产生抗氧化剂以降低 ROS 的毒性细胞浓度。
更新日期:2021-08-17
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