Objective: Circadian rhythm is endogenous 24-hr oscillations usually entrained to the daily environmental cycle of 12/12 h light/dark (LD). It has been reported that disruption of circadian rhythm causes delirium, which is also often developed in patients with advanced cancer. However, the mechanisms by which the progression of cancer disrupts circadian rhythms and ultimately leads to the development of delirium has not been yet understood. We have recently established cancer-induced cachexia model mice by implantation of human stomach cancer cell line 85As2. In this study, we investigated the circadian rhythms of locomotor activity in 85As2-implanted mice.
Methods: 85As2 cells were implanted into 8-week-old male BALB/c nude mice (2x10⁵ cells/mouse). Home-cage activity was measured after 2 weeks from implantation under LD. Mice were then placed in constant darkness (DD) or light (LL), and finally returned to LD cycle. The day-night variation were analyzed using Actogram.
Results: The active phase of 85As2-implanted mice gradually shifted from dark to light between 2 to 4 weeks after implantation, which was almost reversed after 4 weeks. The free-running period under DD or LL condition was significantly shorter compared to the control. Even after returning to LD, the active phase remained reversed in 85As2-implanted mice.
Summary: 85As2-implanted mice demonstrated the reverse of day-night variation without synchronization of photoperiod, and shortened free-running period, suggesting that 85As2-implantation may directly affect the circadian rhythm formation.