Temporal trajectories of novel object recognition performance in mice exposed to intermittent hypoxia

Intermittent hypoxia is one of the major perturbations of sleep-disordered breathing and has been causally implicated in neurocognitive deficits. However, the reversibility of such deficits is unclear. Male C57BL/6J mice were exposed to either intermittent hypoxia or room air for 3-240 days, and then half were randomly selected and allowed to recover in normoxic conditions for the same duration of the previous exposure. A novel object recognition (NOR) test was performed. NOR performance was stable over time in room air. Intermittent hypoxia induced significant reductions in recognition index that progressed over the first 45 days and stabilised thereafter. Normoxic recovery of recognition index was essentially complete and indistinguishable from room air in mice exposed to shorter intermittent hypoxia times (<90 days). However, significant residual deficits emerged after normoxic recovery following prolonged intermittent hypoxia exposures (p<0.01). In addition, gradual attenuation of the magnitude of recovery in recognition index occurred with increasingly longer intermittent hypoxia exposures (MANOVA p<0.0001). Intermittent hypoxia during the resting period reduces NOR performance in a time-dependent fashion. Reversal of NOR performance deficits is unlikely after prolonged intermittent hypoxia duration. These findings suggest that early recognition of sleep apnoea and effective treatment are critical for restoration of the adverse cognitive effects of the disease.