Dim light at night interacts with intermittent hypoxia to alter cognitive and affective responses

Abstract

Obstructive sleep apnea (OSA) and dim light at night (dLAN) have both been independently associated with alterations in mood and cognition. We aimed to determine whether dLAN would interact with intermittent hypoxia (IH), a condition characteristic of OSA, to alter the behavioral, cognitive, and affective responses. Adult male mice were housed in either standard lighting conditions (14:10-h light-dark cycle; 150 lux:0 lux) or dLAN (150 lux:5 lux). Mice were then exposed to IH (15 cycles/h, 8 h/day, FiO2 nadir of 5%) for 3 wk, then tested in assays of affective and cognitive responses; brains were collected for dendritic morphology and PCR analysis. Exposure to dLAN and IH increased anxiety-like behaviors, as assessed in the open field, elevated plus maze, and the light/dark box. dLAN and IH increased depressive-like behaviors in the forced swim test. IH impaired learning and memory performance in the passive avoidance task; however, no differences were observed in spatial working memory, as assessed by y-maze or object recognition. IH combined with dLAN decreased cell body area in the CA1 and CA3 regions of the hippocampus. Overall, IH decreased apical spine density in the CA3, whereas dLAN decreased spine density in the CA1 of the hippocampus. TNF-α gene expression was not altered by IH or lighting condition, whereas VEGF expression was increased by dLAN. The combination of IH and dLAN provokes negative effects on hippocampal dendritic morphology, affect, and cognition, suggesting that limiting nighttime exposure to light in combination with other established treatments may be of benefit to patients with OSA.

Keywords: anxiety; depression; intermittent hypoxia; learning; light at night; memory.

Fig. 1.

The effects of intermittent hypoxia and dim light at night on anxiety and depressive-like behaviors in male mice. Means ± SE number of rears for the first 5 min of an open field test (A) and percent of activity in the center (B) in the open field test of anxiety-like behaviors. Total duration of test was 20 min. Means ± SE percent of time spent in the open arm of the elevated plus maze test for anxiety-like behaviors (C). Total duration of the test was 300 s. Means ± SE total time spent in light side of light-dark box (D) and latency to enter the light side of box (E). Total duration of the test was 300 s. Means ± SE latency to first floating bout in the forced swim test, a measure for depressive-like behavior (F). Total duration of test was 600 s, *P < 0.05 between room air (AIR) and intermittent hypoxia (IH) or light-dark (LD) and dim light at night (dLAN) for all behaviors.

Fig. 2.

The effect of intermittent hypoxia and dim light at night on learning and memory in male mice. Means ± SE latency to enter the dark chamber on day 1 of testing (A) and day 2 of testing (B) of the passive avoidance test. Total duration of test was 300 s. *P < 0.05 between AIR and IH.

Fig. 3.

Body mass was decreased during IH exposure. Means ± SE body mass for duration of IH treatment. *P < 0.05 between AIR and IH.

Fig. 4.

The effect of intermittent hypoxia and dim light at night on adrenal gland masses and corticosterone concentrations in mice. Means ± SE body corrected mass for adrenal glands (A) and means ± SE corticosterone concentrations (B) at end of experiment. *P < 0.05.

Fig. 5.

The effect of intermittent hypoxia and dim light at night on dendritic morphology. Apical spine density of neurons in CA1 (A) and CA3 (D) of the hippocampus (± SE). Basilar spine density of neurons in CA1 (B) and CA3 (E) of the hippocampus ( ± SE). Average cell body area of neurons in the CA1 (C) and CA3 (F) of the hippocampus ( ± SE). *P < 0.05.