Cognitive Function, Sleep, and Neuroinflammatory Markers in Mice Exposed to Very Long-Term Intermittent Hypoxia

Chronic intermittent hypoxia (IH) is one of the hallmark features of obstructive sleep apnea (OSA) and adversely affects neurocognitive and behavioral functioning. However, how the duration of IH correlates with its deleterious effects remains unexplored. We aimed to assess the effects of IH over a prolonged period of time mimicking untreated OSA. Male C57Bl/6J mice were exposed to IH for 96 weeks. Sleep activity was acquired using a piezoelectric system. Novel object recognition (NOR) and the elevated plus maze test (EPMT) were conducted as measures of cognitive function and anxiety, respectively. Brain inflammation was evaluated by a panel of inflammation marker assays. All tests were performed after 16 and 96 weeks of IH exposure. After 96 weeks, sleep percentages during the dark phase decreased in both IH and room air (RA) compared to 16-week exposure (RA: p = 0.0214; IH: p = 0.0188). In addition to age-dependent declines in NOR performance, the mice after 96 weeks of IH exposure had lower NOR preference scores than RA controls (p = 0.0070). The time spent in open arms of the EPMT was reduced in mice exposed to IH compared to RA. Inflammatory marker expression increased in IH-exposed mice. Thus, aging and IH induce similar alterations in sleep, cognition, and neuroinflammation. However, the effects of aging are exacerbated by concurrent IH, suggesting that OSA is a disease associated with an acceleration in biological aging.