Short-term sleep fragmentation enhances anxiety-related behavior: The role of hormonal alterations

Abstract

Introduction The neuroendocrine background of acute sleep fragmentation in obstructive sleep apnea and sleep fragmentation involvement in psychiatric comorbidities, common in these patients, are still largely unknown. The aim of this study was to determine the effects of short-term experimental sleep fragmentation on anxiety -like behavior and hormonal status in rats. Methods Male rats were adapted to treadmill (ON and OFF mode with belt speed set on 0.02m/s and 0.00m/s) and randomized to: 1) treadmill control (TC, only OFF mode); 2) motion, activity control (AC, 10min ON and 30min OFF mode) and 3) sleep fragmentation (SF, 30s ON and 90s OFF mode) group. Six hours later, the animals were tested in the open field, elevated plus maze and light/dark test (n = 8/group). Testosterone, estradiol, progesterone and corticosterone were determined in separate animal cohort immediately upon sleep fragmentation (n = 6/group). Results SF rats showed decreased rearings number, decreased time spent in the central area and increased thigmotaxic index compared to TC and AC rats in the open field test. Similarly, increased anxiety upon sleep fragmentation was observed in the elevated plus maze and the light/dark test. Significantly lower testosterone, estradiol and progesterone levels were determined in SF in comparison to AC and TC groups, while there was no significant difference in the levels of corticosterone. Conclusion Short term sleep fragmentation enhances anxiety-related behavior in rats, which could be partly mediated by the observed hormonal changes presented in the current study in form of testosterone, estradiol and progesterone depletion.

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

“…We have previously shown that sleep deprivation induces anxiety-linked behavior in both humans and animals. On the other hand, there is an association between anxiety and oxidative stress in the brain [ 25 , 33 , 53 – 55 ]. Present results indicated that there is a correlation between oxidative stress byproducts and anxiety behavior of the rats after sleep fragmentation.…”

“…Therefore, the role of sleep fragmentation in the mediation of anxiety in OSA patients seems to be very rational to hypothesize. Indeed, the models of acute sleep fragmentation recently developed in rodents confirmed an effect on cognition, in particular, memory consolidation, brain excitability, and anxiety-related behaviors [ 22 – 25 ]. However, we still do not have clear experimental data on the relationship between sleep fragmentation in OSA and anxiety-linked behavior, nor the underlying molecular mechanisms.…”

Altered sleep behavior in a genetic mouse model of impaired fear extinction

“…In line with human studies, experiments in BL6 mice showed that low REMS continuity at baseline was correlated with higher levels of hyperarousal one month after contextual fear conditioning 46 . Moreover, as a proof of principle, experimentally induced sleep fragmentation led to an increase of anxiety-like behavior in rats 74 . Another study found more spontaneous awakenings in more anxious BALBc/J mice than in BL6 www.nature.com/scientificreports/ controls 75 .…”

Time‐restricted feeding prevents depressive‐like and anxiety‐like behaviors in male rats exposed to an experimental model of shift‐work

“…It is well established that sleep disturbances have negative effects for mental health (McCoy & Strecker, 2011). In animal models, sleep disturbances induce anxiety‐like behaviors (Grubac et al., 2019; Silva et al., 2004) and depressive‐like behaviors (Gonzalez‐Castañeda et al., 2016; Wang et al, 2017). In this regard, the possible effect of our simulated shift‐work protocol on sleep patterns and its association with the development of depressive and anxiety‐like behaviors as observed in W‐AL rats could not be discarded.…”