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

Clementine Puech; Mohammad Badran; Alexandra R Runion; Max B Barrow; Zhuanhong Qiao; Abdelnaby Khalyfa; David Gozal

doi:10.1016/j.nbscr.2022.100084

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

Neurobiol Sleep Circadian Rhythms. 2022 Oct 10:13:100084. doi: 10.1016/j.nbscr.2022.100084. eCollection 2022 Nov.

Authors

Clementine Puech¹, Mohammad Badran¹, Alexandra R Runion², Max B Barrow², Zhuanhong Qiao¹, Abdelnaby Khalyfa¹, David Gozal¹

Affiliations

¹ Child Health Research Institute, Department of Child Health, School of Medicine, University of Missouri, Columbia, MO, USA.
² Undergraduate Student Research Program, University of Missouri, Columbia, MO, USA.

Abstract

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 FiO₂ 21% 90 seconds-6.3% 90s or room air (RA; FiO₂ 21%) 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.

Keywords: Behaviors; Elevated plus maze test; Forced swimming test; Intermittent hypoxia; Novel object recognition; Obstructive sleep apnea; Sleep fragmentation.