Heterotopic 4T1 breast cancer transplantation induces hippocampal inflammation and depressive-like behaviors in mice

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.