Assessment of depressive and/or anxious behavior in mice subjected to colorectal carcinogenesis

Abstract

Colorectal cancer (CRC) patients usually present high levels of depression and anxiety. These comorbidities impair the adherence to cancer treatment, patients's quality of life and long-term survival. Despite the evidence that cytokines are involved in the pathophysiology of depression and anxiety in cancer patients, these relationships are poorly understood. In the present study, using an experimental model of colorectal carcinogenesis induced by MNNG, we will study the influence of cytokines on brain activity, identified by immunostaining of c-Fos, which is a marker of neuronal activity, in brain regions related to the manifestation of depression and anxiety (amygdala, prefrontal cortex and hippocampus). Behavioral changes will be evaluated by sucrose preference, elevated plus maze, and forced swimming tests. Cerebral and colon production of IL-1, IL-6, IL-8, IL-10, IL-12, TGF-², TNF-±, and the chemokine CX3CL1 (fractalkine), will be evaluated by ELISA. To evaluate the prognostic potential of these molecules in identifying the risk of manifestation of psychological changes, the analysis will be performed 8 weeks (initial tumorigenesis) and 20 weeks (advanced tumorigenesis) after tumor induction. An integral understanding of the immune system function in the pathogenesis of anxiety and depression in cancer patients will allow the development of new interventions that lead to an improved quality of life and overall survival of CRC patients.