REM sleep’s unique associations with corticosterone regulation, apoptotic pathways, and behavior in chronic stress in mice

Abstract

One of sleep’s putative functions is mediation of adaptation to waking experiences. Chronic stress is a common waking experience; however, which specific aspect of sleep is most responsive, and how sleep changes relate to behavioral disturbances and molecular correlates remain unknown. We quantified sleep, physical, endocrine, and behavioral variables, as well as the brain and blood transcriptome in mice exposed to 9 weeks of unpredictable chronic mild stress (UCMS). Comparing 46 phenotypic variables revealed that rapid–eye-movement sleep (REMS), corticosterone regulation, and coat state were most responsive to UCMS. REMS theta oscillations were enhanced, whereas delta oscillations in non-REMS were unaffected. Transcripts affected by UCMS in the prefrontal cortex, hippocampus, hypothalamus, and blood were associated with inflammatory and immune responses. A machine-learning approach controlling for unspecific UCMS effects identified transcriptomic predictor sets for REMS parameters that were enriched in 193 pathways, including some involved in stem cells, immune response, and apoptosis and survival. Only three pathways were enriched in predictor sets for non-REMS. Transcriptomic predictor sets for variation in REMS continuity and theta activity shared many pathways with corticosterone regulation, in particular pathways implicated in apoptosis and survival, including mitochondrial apoptotic machinery. Predictor sets for REMS and anhedonia shared pathways involved in oxidative stress, cell proliferation, and apoptosis. These data identify REMS as a core and early element of the response to chronic stress, and identify apoptosis and survival pathways as a putative mechanism by which REMS may mediate the response to stressful waking experiences.

Loss of Arc attenuates the behavioral and molecular responses for sleep homeostasis in mice

“…At this time, the mechanism for REM sleep regulation through Arc is unclear. It might be related to the phenomenon that "stress" tends to increase REM sleep (33,34). Further studies are required to elucidate the Arc-mediated regulation of REM sleep.…”

Psychological Stress: A Predisposing and Exacerbating Factor in Periodontitis

“…Reductions in sleep time have been shown to be associated with higher reported stress levels the next day [82]. Conversely, chronic stress has been associated with reduced time spent in REM sleep [83,84]. Early life stress is associated with insomnia [85,86] and can result in increased serum concentrations of inflammatory cytokines [14,57,87].…”

Chronic antidepressant treatments rescue reduced REM sleep theta power in a rat social defeat stress model of depression

“…In the other mouse SDS model [Henderson et al, 2017], REM sleep durations and bouts decreased and REM sleep theta power remained unchanged during the light phase. In the UCMS model [Nollet et al, 2019], REM sleep duration, bouts, and theta power (per day) increased during the 9-week UCMS. In the WIRS model [Yasugaki et al, 2019], REM sleep duration and bouts during the dark phase increased during the first week of the stress episode.…”

“…A pioneering study by Hegde et al investigated the effects of 2-hr chronic immobilization stress (CIS) for 10 days on REM sleep theta oscillation and found that a subgroup of stressed rats showed increased REM sleep durations in association with attenuated REM sleep theta powers [Hegde et al, 2011]. Recently, four independent studies, using mouse SDS [Wells et al, 2017;Henderson et al, 2017], unpredictable chronic mild stress (UCMS) [Nollet et al, 2019], and water immersion and restraint stress (WIRS) [Yasugaki et al, 2019] models, have shown that these stresses induced changes in various REM sleep parameters. These changes, however, were observed mostly during the stress periods and little was observed in terms of post-stress effects (only 5 days after the last SDS [Wells et al, 2017;Henderson et al, 2017]).…”