Explicit memory, anxiety and depressive like behavior in mice exposed to chronic intermittent hypoxia, sleep fragmentation, or both during the daylight period

Oct 18, 2022Neurobiology of sleep and circadian rhythms

Memory, anxiety, and depression-like behavior in mice exposed to repeated low oxygen, sleep disruption, or both during the day

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Abstract

Obstructive sleep apnea is associated with distinct cognitive and anxiety-related behavior changes in mice.

Sleep fragmentation impaired cognitive performance in a novel object recognition test.
Intermittent hypoxia also led to cognitive deficits but increased anxiety behaviors.
Combined sleep fragmentation and intermittent hypoxia did not worsen cognitive performance compared to each condition alone.
The combination of sleep fragmentation and intermittent hypoxia canceled out the effects on anxiety behaviors.
Differential mechanisms may underlie the cognitive and anxiety-related effects of sleep fragmentation and intermittent hypoxia.

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Obstructive sleep apnea (OSA) is a chronic and highly prevalent condition characterized by chronic intermittent hypoxia (IH) and sleep fragmentation (SF), and can lead to a vast array of end-organ morbidities, particularly affecting cardiovascular, metabolic and neurobehavioral functioning. OSA can induce cognitive and behavioral and mood deficits. Male C57Bl/6J 8-week-old mice were housed in custom-designed cages with a silent motorized mechanical sweeper traversing the cage floor at 2-min intervals (SF) during daylight for four weeks. Sleep control (SC) consisted of keeping sweeper immobile. IH consisted of cycling FiO21% 90 seconds-6.3% 90s or room air (RA; FiO21%) for sixteen weeks and combined SF-IH was conducted for nine weeks. Open field novel object recognition (NOR) testing, elevated-plus maze test (EPMT), and forced swimming test (FST) were performed. SF induced cognitive NOR performance impairments in mice along with reduced anxiety behaviors while IH induced deficits in NOR performance, but increased anxiety behaviors. SF-IH induced impaired performance in NOR test of similar magnitude to IH or SF alone. Combined SF-IH exposures did not affect anxiety behaviors. Thus, both SF an IH altered cognitive function while imposing opposite effects on anxiety behaviors. SF-IH did not magnify the detrimental effects of isolated SF or IH and canceled out the effects on anxiety. Based on these findings, the underlying pathophysiologic processes underlying IH and SF adverse effects on cognitive function appear to differ, while those affecting anxiety counteract each other. 2 2

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Explicit memory, anxiety and depressive like behavior in mice exposed to chronic intermittent hypoxia, sleep fragmentation, or both during the daylight period

Abstract

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