Barbetti Margherita, Smiley Cora E, Savi Monia, Sgoifo Andrea, Wood Susan K, Carnevali Luca
Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Parma, Italy.
Department of Pharmacology, Physiology, and Neuroscience, University of South Carolina School of Medicine, Columbia, SC, 29209, USA.
Neurobiol Stress. 2025 Aug 12;38:100751. doi: 10.1016/j.ynstr.2025.100751. eCollection 2025 Sep.
Exposure to stress has widespread pathological consequences in terms of neuropsychiatric disorders and cardiovascular disease. Psychosocial stressors represent the most highly impactful and commonly experienced form of stress and, in preclinical studies, have been found to induce distinct overlapping immune and cardiovascular alterations. Historically, the social defeat model has been fundamental in providing insights into the autonomic and neuroimmune mediators of cardiovascular dysfunction in the face of social stress exposure. However, this procedure relies on aggressive, physical interaction between rodents and is limited by its almost exclusive application to young adult males. This challenges the possibility of using social defeat to generate data in rodents that can be translated into social stress-related processes in both men and women across the lifespan. More recently, a novel vicarious social defeat procedure has been developed, wherein a rodent bears witness to an aggressive social defeat encounter between two males from the safety of an adjacent compartment. This review first discusses the existing data regarding stress-induced cardiovascular alterations and the underlying autonomic and neuroimmune mediators of social defeat while critically discussing the limitations of this model. New prospects are then offered based on recent findings across a diverse population of rodent species, sexes, and ages to support the use of vicarious/witness social defeat model as an optimal strategy to investigate social stress-related autonomic, neuroimmune, and cardiovascular processes using more comprehensive and inclusive methods.
暴露于应激会在神经精神疾病和心血管疾病方面产生广泛的病理后果。心理社会应激源是最具影响力且最常经历的应激形式，在临床前研究中，已发现其会诱发独特的重叠性免疫和心血管改变。从历史上看，社会挫败模型对于深入了解面对社会应激暴露时心血管功能障碍的自主神经和神经免疫介质至关重要。然而，该程序依赖于啮齿动物之间的攻击性身体互动，并且几乎仅适用于年轻成年雄性，这限制了其应用。这对利用社会挫败在啮齿动物中生成可转化为不同年龄段男性和女性社会应激相关过程的数据的可能性提出了挑战。最近，一种新型的替代性社会挫败程序已被开发出来，即一只啮齿动物从相邻隔室的安全位置见证两只雄性之间的攻击性社会挫败遭遇。本综述首先讨论了关于应激诱导的心血管改变以及社会挫败潜在的自主神经和神经免疫介质的现有数据，同时批判性地讨论了该模型的局限性。然后根据最近在不同啮齿动物物种、性别和年龄群体中的研究结果提供新的前景，以支持使用替代性/见证性社会挫败模型作为一种最佳策略，采用更全面和包容的方法来研究与社会应激相关的自主神经、神经免疫和心血管过程。
