越来越多的证据表明，人类和啮齿动物的社会隔离（SI）与癌症发病率和死亡率的增加有关，但其中的调节机制仍然难以捉摸。在这里，我们研究了 SI 的神经内分泌和免疫学后果及其对幼鼠和荷癌大鼠的短期和长期生理影响。研究结果表明，与对照组相比，隔离动物的体重显着下降。具体来说，雌性在隔离的第一周体重明显下降。离体大鼠的 MADB106 实验性肺转移数量显着增加。尽管离体荷瘤大鼠的死亡率较高，但出乎意料的是，它们表现出原位植入的 MADB106 肿瘤的生长速度降低。这些切除的肿瘤的转录组分析表明各种基因的表达显着下调，包括那些与促转移过程（例如 EMT）相关的基因。在初始大鼠（无癌症）中，SI 条件下 IL-6 水平升高，总 IgG 水平降低。研究发现 TNFα 具有混合效应，在女性中增加，在男性中减少。在中枢神经系统中，分离的大鼠在与压力反应和社会行为相关的关键大脑区域中显示出基因表达的改变。丘脑的室旁核以及终纹的床核成为显着受影响的区域。观察到催产素、血清素和多巴胺受体表达的变化。离体大鼠还表现出下丘脑-垂体-肾上腺（HPA）轴相关调节的更大改变以及血浆 CORT 水平的增加。我们的研究强调了 SI 对转移过程的深远影响。此外，还讨论了 SI 对体温调节的潜在有害影响，强调了社会体温调节在维持生理稳定性方面的重要性，并强调了在研究中避免单一笼养做法的必要性。我们报告了神经免疫相互作用和大脑基因表达的变化，强调需要进一步研究这些潜在过程，以改善动物模型的结果，并通过增加社会支持对癌症患者进行潜在干预。版权所有 © 2024。由爱思唯尔公司出版。

Accumulating evidence indicates that social isolation (SI) in humans and rodents is associated with increased cancer incidence and mortality, yet mediating mechanisms remain elusive. Here, we examine the neuroendocrine and immunological consequences of SI and its short- and long-term physiological impacts in naïve and cancer-bearing rats. Findings indicate that isolated animals experienced a significant decrease in weight compared to controls. Specifically, females showed a marked weight decrease during the first week of isolation. Isolated rats had significantly higher numbers of MADB106 experimental pulmonary metastases. Although mortality rates were higher in isolated tumor-bearing rats, unexpectedly, they exhibited a reduced growth rate of orthotopically implanted MADB106 tumors. Transcriptomic analyses of these excised tumors indicated a major downregulation in the expression of various genes, including those associated with pro-metastatic processes (e.g., EMT). In naïve rats (no cancer), levels of IL-6 increased, and total IgG levels decreased under SI conditions. A mixed effect was found for TNFα, which increased in females and decreased in males. In the central nervous system, isolated rats showed altered gene expression in key brain regions associated with stress responses and social behavior. The paraventricular nucleus of the thalamus emerged as a significantly affected region, along with the bed nucleus of the stria terminalis. Changes were observed in the expression of oxytocin, serotonin, and dopamine receptors. Isolated rats also exhibited greater alterations in hypothalamic-pituitary-adrenal (HPA) axis-related regulation and an increase in plasma CORT levels. Our study highlights the profound impact of SI on metastatic processes. Additionally, the potential detrimental effects of SI on thermoregulation were discussed, emphasizing the importance of social thermoregulation in maintaining physiological stability and highlighting the need to avoid single-caging practices in research. We report neuro-immune interactions and changes in brain gene expression, highlighting the need for further research into these underlying processes to improve outcomes in animal models and potential interventions for cancer patients through increased social support.Copyright © 2024. Published by Elsevier Inc.