社会隔离对神经内分泌免疫状态及大鼠癌症进展的有害影响

累积的证据表明，社会隔离（SI）与人类和啮齿动物中癌症发生率和死亡率增加有关，但其机制尚不明确。本研究考察了社会隔离的神经内分泌和免疫学后果，以及其对无癌和患癌大鼠的短期与长期生理影响。结果显示，孤立动物的体重明显低于对照组，尤其在第一周内，雌性动物体重下降更为显著。孤立大鼠的MADB106实验性肺转移灶数量显著增加。尽管孤立的肿瘤携带大鼠的死亡率较高，但意外地，它们的异位移植MADB106肿瘤的生长速率反而较低。对这些切除肿瘤的转录组分析显示，包括与转移促进相关的基因（如EMT）在内的多种基因表达显著下调。在无癌的大鼠（无癌模型）中，IL-6水平升高，血清总IgG水平下降。TNFα表现出混合效应，在雌性中升高，在雄性中下降。在中枢神经系统中，孤立大鼠在应激反应和社会行为相关的关键脑区表现出基因表达变化。丘脑旁核和束状核被发现受影响最为显著，氧酸运激素、血清素及多巴胺受体的表达也发生变化。孤立大鼠在下丘脑-垂体-肾上腺（HPA）轴调节方面出现更大变化，血浆CORT水平升高。本研究强调社会隔离对转移过程的深远影响，并讨论了其对体温调节的潜在有害作用，强调社会热调节在维持生理稳定中的重要性，并指出应避免动物实验中采用单笼饲养。我们报告了神经免疫相互作用及脑内基因表达的变化，强调需要进一步研究这些基础机制，以改善动物模型的预后和为癌症患者提供通过增加社会支持的潜在干预措施。

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.