Anxiogenic Potential of Experimental Sleep Fragmentation Is Duration-Dependent and Mediated via Oxidative Stress State.

Željko Grubač,Dragan Hrnčić,Tatjana Simić,Djurdja Jerotić,Nikola Šutulović,Nela Puškaš,Olivera Stanojlović,Djuro Macut,Aleksandra Rašić-Marković,Sonja Šuvakov,Laura Bravo

doi:10.1155/2021/2262913

Željko Grubač, Dragan Hrnčić + Show 9 more

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https://doi.org/10.1155/2021/2262913

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Abstract

Sleep architecture alterations, among which sleep fragmentation is highly prevalent, represent risk factors for a variety of diseases, ranging from cardiovascular to brain disorders, including anxiety. What mediates anxiety occurrence upon sleep fragmentation is still a matter of debate. We hypothesized that the sleep fragmentation effects on anxiety are dependent on its duration and mediated by increased oxidative stress and alterations in the number of parvalbumin (PV+) interneurons in the hippocampus. Sleep was fragmented in rats by the treadmill method during a period of 14 days (SF group). Rats with undisturbed sleep in the treadmill (TC group) and those receiving equal amounts of treadmill belt motion (EC group) served as controls. To assess anxiety, we subjected rats to the open field, elevated plus maze, and light-dark tests on the 0, 7th, and 14th day. Upon the last test, brain structures were sampled for oxidative stress assessment and PV+ interneuron immunohistochemistry. The results of ethological tests of anxiety-linked behavior suggested duration-dependent anxiogenic potential of sleep fragmentation. Rats' anxiety-linked behavior upon sleep fragmentation significantly correlated with oxidative stress. The rats with fragmented sleep (SF) showed significantly higher oxidative stress in the hippocampus, thalamus, and cortex, compared to controls (TC and EC), while the antioxidant enzymes' activity was significantly decreased. No significant differences were observed in hippocampal PV+ interneurons among these groups. Our results showed that duration of sleep fragmentation is a significant determinant of anxiety-linked behavior, and these effects are mediated through oxidative distress in the brain. Herein, it is revealed that the sleep fragmentation-oxidative stress-anxiety axis contributes to our better understanding of pathophysiological processes, occurring due to disrupted sleep patterns.

Highlights

Sleep is a vital physiological process widely preserved during phylogenies, indicating its utmost importance for the functioning of the whole organism
Quantitative evaluation of the anxiety-linked parameters in the open field test showed no differences within the treadmill control (TC) group over time in any of the investigated output parameters (0, 7, and 14 days, p > 0:5, Figure 3)
The results of the open field, elevated plus maze, and lightdark tests, ethological tests of anxiety-linked behavior, performed in this study suggested a duration-dependent anxiogenic potential of sleep fragmentation

Summary

Introduction

Sleep is a vital physiological process widely preserved during phylogenies, indicating its utmost importance for the functioning of the whole organism. Sleep disorders are widely prevalent in the general population and include alterations in quantity and quality of sleep [1]. In contrast to total sleep deprivation, sleep fragmentation is the set of frequent arousals, restructuring the basic sleeping architecture, rather than the loss of total sleep time [2, 3]. It appears as daytime somnolence, and it adversely affects mood, cognition, and memory [4, 5].

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