Shift work schedules alter immune cell regulation and accelerate cognitive impairment during aging
Abstract
Background: Disturbances of the sleep-wake cycle and other circadian rhythms typically precede the age-related deficits in learning and memory, suggesting that these alterations in circadian timekeeping may contribute to the progressive cognitive decline during aging. The present study examined the role of immune cell activation and inflammation in the link between circadian rhythm dysregulation and cognitive impairment in aging.
Methods: C57Bl/6J mice were exposed to shifted light-dark (LD) cycles (12 h advance/5d) during early adulthood (from ≈ 4-6mo) or continuously to a "fixed" LD12:12 schedule. At middle age (13-14mo), the long-term effects of circadian rhythm dysregulation on cognitive performance, immune cell regulation and hippocampal microglia were analyzed using behavioral, flow cytometry and immunohistochemical assays.
Results: Entrainment of the activity rhythm was stable in all mice on a fixed LD 12:12 cycle but was fully compromised during exposure to shifted LD cycles. Even during "post-treatment" exposure to standard LD 12:12 conditions, re-entrainment in shifted LD mice was marked by altered patterns of entrainment and increased day-to-day variability in activity onset times that persisted into middle-age. These alterations in light-dark entrainment were closely associated with dramatic impairment in the Barnes maze test for the entire group of shifted LD mice at middle age, well before cognitive decline was first observed in aged (18-22mo) animals…
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