Yan Wenjing, Zhu Hulin, Zhang Pengbo, Sun Ting, Gong Shuai, Sun Guoxiu, Ren Zeqiang
School of Nursing, Xuzhou Medical University, Xuzhou, China.
Department of Stomatology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.
Metab Brain Dis. 2022 Dec;37(8):2955-2963. doi: 10.1007/s11011-022-01058-6. Epub 2022 Aug 10.
Cancer and its accompanying treatments can lead to numerous physical and emotional concerns, including subclinical or clinical depression and anxiety, which could significantly impact one's well-being, quality of life, and survival. A large number of studies have elucidated that neuroinflammation is associated with depression. Here, we report the hippocampal pathological changes and depressive behaviors of a heterotopic breast cancer transplantation mouse model; hence, a heterotopic 4T1 breast cancer transplantation mouse model was established. Assessment of cognitive and locomotive functions of the experimental animals was conducted using open- and closed-field tests, including a tail suspension test. Expression levels of monoaminergic system markers, brain-derived neurotrophic factor (BDNF), pro-inflammatory cytokines, and nuclear factor-kappa B (NFκB) in the hippocampus and serum were detected using immunochemistry and western and enzyme-linked immunosorbent assay analysis. A comparison of the differences between model and control animals was performed. As per our findings, 4T1 tumor-bearing mice displayed cancer-related anorexia/cachexia with significant reductions in the travel distance and the total number of squares crossed in the open- and closed-field tests. Additionally, the 4T1 tumor-bearing mice withstood a more extended period of immobility during the tail suspension test. Immunohistochemistry studies revealed reduced levels of serotonin, norepinephrine, and BDNF in the hippocampus and serum. Elevated levels of NFκB and pro-inflammatory cytokines in the hippocampus were also observed. These findings suggest that hippocampal inflammation may have played an important role in the neurological function and depressive behavior in heterotopic 4T1 breast cancer transplantation mice.
癌症及其伴随的治疗可能导致许多身体和情绪问题，包括亚临床或临床抑郁症和焦虑症，这可能会显著影响一个人的幸福感、生活质量和生存期。大量研究表明神经炎症与抑郁症有关。在此，我们报告了异位乳腺癌移植小鼠模型的海马病理变化和抑郁行为；因此，建立了异位4T1乳腺癌移植小鼠模型。使用旷场试验和封闭场试验（包括悬尾试验）对实验动物的认知和运动功能进行评估。使用免疫化学、蛋白质印迹法和酶联免疫吸附测定分析法检测海马体和血清中单胺能系统标志物、脑源性神经营养因子（BDNF）、促炎细胞因子和核因子-κB（NFκB）的表达水平。对模型动物和对照动物之间的差异进行了比较。根据我们的研究结果，携带4T1肿瘤的小鼠出现了与癌症相关的厌食/恶病质，在旷场试验和封闭场试验中，行进距离和穿过的方格总数显著减少。此外，在悬尾试验中，携带4T肿瘤的小鼠能耐受更长时间的不动状态。免疫组织化学研究显示，海马体和血清中血清素、去甲肾上腺素和BDNF的水平降低。还观察到海马体中NFκB和促炎细胞因子水平升高。这些发现表明，海马体炎症可能在异位4T1乳腺癌移植小鼠的神经功能和抑郁行为中起重要作用。
