Circadian Regulation of the Neuroimmune Environment Across the Lifespan: From Brain Development to Aging

Circadian clocks confer 24-h periodicity to biological systems, to ultimately maximize energy efficiency and promote survival in a world with regular environmental light cycles. In mammals, circadian rhythms regulate myriad physiological functions, including the immune, endocrine, and central nervous systems. Within the central nervous system, specialized glial cells such as astrocytes and microglia survey and maintain the neuroimmune environment. The contributions of these neuroimmune cells to both homeostatic and pathogenic demands vary greatly across the day. Moreover, the function of these cells changes across the lifespan. In this review, we discuss circadian regulation of the neuroimmune environment across the lifespan, with a focus on microglia and astrocytes. Circadian rhythms emerge in early life concurrent with neuroimmune sculpting of brain circuits and wane late in life alongside increasing immunosenescence and neurodegeneration. Importantly, circadian dysregulation can alter immune function, which may contribute to susceptibility to neurodevelopmental and neurodegenerative diseases. In this review, we highlight circadian neuroimmune interactions across the lifespan and share evidence that circadian dysregulation within the neuroimmune system may be a critical component in human neurodevelopmental and neurodegenerative diseases.