Effects of constant darkness on behavior and physiology of male and female mice.

A healthy state of life suggests not only a disease-free condition but also normal psychological functioning and behavior. To maintain a healthy life, the duration of light exposure is a crucial factor. Perturbation of the standard light-dark cycle (LD: 12h light-12 h dark in mice) may result in brain, behavioral, and physiological abnormalities. The current study determined the effects of three weeks and five weeks of constant darkness (DD: 00h light-24h dark) on the behavior, hormones, prefrontal cortex (PFC), and metabolome of male and female C57BL/6J mice. We also studied three weeks of restoration in LD following five weeks of DD exposure. The results revealed that three weeks of DD affected male mice more than females, and five weeks of DD had a comparable impact on behavior, hormones, and the PFC of male and female mice. After restoration in LD, the DD-induced changes reverted to time-matched LD conditions in male and female mice. Furthermore, metabolome analysis corroborated male and female mice's behavioral and molecular kinetics. The present study laid the foundation for understanding how DD affects behavior and the PFC as a function of a) time- and b) sex and described the roles of stress and sex hormones, cytokines, neurotrophins, and metabolic pathways.