The effects of exercise and quercetin on insulin-like growth factor-۱ as a possible mediator in depression caused by dimethylhydrazine-induced colon cancer in rats

In addition to physical problems, depression is one of the most important challenges for patients with various types of cancer, especially colorectal cancer. Modulation of brain neurotrophic factors is the key link between cancer and depression. In this study, we evaluated the effects of Quercetin and exercise on depressive behaviors in rats with colon cancer induced by ۱,۲-dimethylhydrazine-induced (DMH) and investigated possible mechanisms. The animals were divided into five groups: ۱. Control group, ۲- Cancer group (by injection of ۲۰ mg/kg DMH, subcutaneous injection, once a week for ۱۰ weeks), ۳- Cancer group and Quercetin (۵۰ mg/kg ۱, gavage once a week for ۱۲ weeks ۴. Cancer group and moderate-intensity training for ۱۲ weeks, ۵- Cancer group with Quercetin and exercise treatment for ۱۲ weeks. Rats receiving DMH showed more depressive behaviors in the forced swim test and the open field test. Histopathological experiments showed nerve damage and reduction of Nissl bodies in the Prefrontal cortex. In addition, injection of DMH increased the serum levels of insulin-like growth factor (IGF-۱) as well as, in tumor tissue and decreased expression of brain-derived neurotrophic factor (BDNF), β-tyrosine kinase receptor (TrKβ), and β-catenin in the Prefrontal cortex. In contrast, Quercetin treatment and exercise had antidepressant effects and increased BDNF expression by modulating IGF-۱ in the peripheral circulation and its augmentation in the brain. All behavioral and histopathological related cases were also reduced. The results show that a combination of Quercetin and exercise, by modulating the amount of IGF-۱ in the peripheral circulation and its increase in the brain regulates the BDNF signaling pathway in the Prefrontal cortex of the brain and exerts anti-tumor and anti-depressant effects.

Keywords:

Brain-derived neurotrophic factor , Prefrontal cortex , rat , colon cancer