Acute Circadian Disruption Due to Constant Light Promotes Caspase 1 Activation in the Mouse Hippocampus

Abstract

In mammals, the circadian system controls various physiological processes to maintain metabolism, behavior, and immune function during a daily 24 h cycle. Although driven by a cell-autonomous core clock in the hypothalamus, rhythmic activities are entrained to external cues, such as environmental lighting conditions. Exposure to artificial light at night (ALAN) can cause circadian disruption and thus is linked to an increased occurrence of civilization diseases in modern society. Moreover, alterations of circadian rhythms and dysregulation of immune responses, including inflammasome activation, are common attributes of neurodegenerative diseases, including Alzheimer’, Parkinson’s, and Huntington’s disease. Although there is evidence that the inflammasome in the hippocampus is activated by stress, the direct effect of circadian disruption on inflammasome activation remains poorly understood. In the present study, we aimed to analyze whether exposure to constant light (LL) affects inflammasome activation in the mouse hippocampus. In addition to decreased circadian power and reduced locomotor activity, we found cleaved caspase 1 significantly elevated in the hippocampus of mice exposed to LL. However, we did not find hallmarks of inflammasome priming or cleavage of pro-interleukins. These findings suggest that acute circadian disruption leads to an assembled “ready to start” inflammasome, which may turn the brain more vulnerable to additional aversive stimuli.

Keywords

• circadian disruption
• constant light
• inflammasomes
• caspase 1
• interleukins
• hippocampus