Mammary tumors compromise time-of-day differences in hypothalamic gene expression and circadian behavior and physiology in mice

Publication date: Available online 17 May 2019Source: Brain, Behavior, and ImmunityAuthor(s): Kyle A. Sullivan, Savannah R. Bever, Daniel B. McKim, Jonathan P. Godbout, John F. Sheridan, Karl Obrietan, Leah M. PyterAbstractCircadian rhythms influence various aspects of biology, including hormonal, immunological, and behavioral processes. These 24-hour oscillations are necessary to optimize cellular functions and to synchronize these processes with the environment. Breast cancer patients and survivors frequently report disruptions in circadian oscillations that adversely affect quality-of-life, including fragmented sleep-wake cycles and flattened cortisol rhythms, which are associated with negative behavioral comorbidities (e.g., fatigue). However, the potential causal role of tumor biology in circadian dysregulation has not been investigated. Here, we examined the extent to which sham surgery, non-metastatic mammary tumors, or mammary tumor removal in mice disrupts circadian rhythms in brain clock gene expression, locomotor behavior (free-running and entrained), and physiological rhythms that have been associated with cancer behavioral comorbidities. Tumors and tumor resection altered time-of-day differences in hypothalamic expression of eight circadian-regulated genes. The onset of activity in entrained running behavior was advanced in tumor-bearing mice, and the amplitude of free-running rhythms was increased in tumor-resected mice. Tumors flattened rhythms in circulating c...
Source: Brain, Behavior, and Immunity - Category: Neurology Source Type: research