Novel effects of vericiguat, alone and combined with high-intensity interval training, on brain function in mice with...

Breast cancer is one of the most common types of cancer in women. High-intensity interval training (HIIT) and vericiguat, as therapeutic methods, have the potential to reduce and improve pathological conditions, as well as mitigate the side effects of standard treatments. Therefore, this study investigated the combined impact of HIIT and vericiguat on anxiety-related behaviors, motor activity, social interactions, and pathological changes in a female mouse model with breast cancer. In this experimental study, 70 female mice were randomly divided into seven groups: a control group (PBS), a breast cancer group (BC) (a mouse model of 4T1 breast cancer), a treatment control group (Vehicle), a group that performed HIIT, a group treated with vericiguat (administered orally for 6 weeks), and a group that performed HIIT and treated with vericiguat. Anxiety-like and social behaviors were assessed. Also, histopathological indicators, tumor volume, and survival rate were evaluated. The results showed that the BC group had a lower open arm time (OAT) (p < 0.05) and open arm entrance (OAE) (P < 0.05) indiced in the elevated plus maze (EPM) test and lower motor activity (P < 0.001) in the open field test (OFT) compared with PBS group, which indicated higher levels of anxiety. In addition, disturbance in the social behavior was seen in BC. The HIIT, vericiguat, and their combination improved these indices. Histopathologically, the HIIT and vericiguat groups showed lower tumor cellularity, mitotic index, metastasis, and higher necrotic foci, compared to the BC group. In conclusion, These findings suggest a potential synergistic benefit of HIIT and vericiguat in modulating behavioral and tumor-related brain pathology in breast cancer.