Combination of quercetin and exercise training attenuate depression in rats with DMH induced colorectal cancer: Possible involvement of inflammation and BDNF signaling.

What is the central question of this study? This study aimed to answer the question that has the combination of exercise training and Quercetin supplementation alleviative effects on the colorectal cancer-related depression in rats with DMH-induced colorectal cancer and what was the corresponding signaling pathway. What is the main finding and its importance? We showed that combination of exercise training and Quercetin supplementation resulted in the significant improvement in depressive-live behaviors and decrease in tumor incidence through modulation of BDNF/ TrKβ /β-catenin axis in the prefrontal cortex. ABSTRACT: In addition to physical problems, depression is considered as one the most important challenges for patients with various cancer types, particularly colorectal cancer. Inflammation and upregulation of brain neurotrophic factors are two major link between cancer and depression. Therefore, this study aimed to evaluate the alleviative effects of quercetin and exercise training on depressive- like behaviors in rats with 1,2-dimethyhydrazine (DMH)-induced colorectal cancer and investigate their underlying mechanisms. Animals were assigned into five groups. Group 1 served as control, group 2 was received DMH (20 mg/kg s.c., once a week for 10 weeks), group 3 was given quercetin (50 mg/kg orally, once per week), group 4 was performed exercise training and group 5 received quercetin and performed exercise for 12 consecutive weeks. DMH-treated rats showed an increase in both depressive-like behaviors in open-field and forced swimming tests. Histopathological examination revealed neural damages and decreased Nissl bodies in prefrontal cortex. In addition, DMH administration increased inflammatory cytokines in the serum cortical and tumor tissues, as well as decreased the expression levels of brain-derived neurotrophic factor, tyrosine kinase β receptor and β-catenin in the cortex. On the other hand, treatment with quercetin and exercise training effectively alleviated all mentioned DMH-associated behavioral, biochemical, and histopathological alterations without changing its antitumor activity. Taken together, our results showed that quercetin and exercise training exerts potent anti-tumor and anti-depressive effects through suppressing inflammation and upregulation of BDNF/ TrKβ /β-catenin axis in the prefrontal cortex. This article is protected by copyright. All rights reserved.