Abstract
In this study, we investigated autophagy, glial activation status, and corticotropin releasing factor (CRF) signaling in the brains of mice after 5 days of sleep fragmentation (SF). Three different brain regions including the striatum, hippocampus, and frontal cortex were selected for examination based on roles in sleep regulation and sensitivity to sleep disruption. For autophagy, we monitored the levels of various autophagic induction markers including beclin1, LC3II, and p62 as well as the levels of lysosomal associated membrane protein 1 and 2 (LAMP1/2) and the transcription factor EB (TFEB) which are critical for lysosome function and autophagy maturation stage. For the status of microglia and astrocytes, we determined the levels of Iba1 and GFAP in these brain regions. We also measured the levels of CRF and its cognate receptors 1 and 2 (CRFR1/2). Our results showed that 5 days of SF dysregulated autophagy in the striatum and hippocampus but not in the frontal cortex. Additionally, 5 days of SF activated microglia in the striatum but not in the hippocampus or frontal cortex. In the striatum, CRFR2 but not CRFR1 was significantly increased in SF-experienced mice. CRF did not alter its mRNA levels in any of the three brain regions assessed. Our findings revealed that autophagy processes are sensitive to short-term SF in a region-specific manner and suggest that autophagy dysregulation may be a primary initiator for brain changes and functional impairments in the context of sleep disturbances and disorders.
Highlights
Insufficient sleep time and/or poor quality of sleep are prevalent in modern society due to factors including excessive workloads and high social competition
Our results suggest that autophagy is sensitive to short-term sleep disturbance and suggest that autophagy dysregulation may be involved in brain impairments in the context of sleep disturbances and disorders
We explored the effects of short-term sleep disturbance on autophagy, functional status of microglia and astrocytes, and corticotropin releasing factor (CRF) signaling in the brain
Summary
Insufficient sleep time and/or poor quality of sleep are prevalent in modern society due to factors including excessive workloads and high social competition. Basal and constituent levels of autophagy are critical for cellular homeostasis because they eliminate nonfunctional biomolecules and damaged organelles inside cells Under challenging conditions such as nutrient depletion or temperature and oxidative stress, autophagy can be induced to degrade certain biomolecules to coordinate metabolic and biogenesis processes that help to ensure cell survival [10]. Microglia may undergo morphological changes accompanied by upregulation in various neuroimmune pathways, which lead to increased production and release of a plethora of chemokines and cytokines including TNFα, IL6, and IL1β. These inflammatory mediators act on neighboring neurons and modulate their excitability [15,16]. Our results suggest that autophagy is sensitive to short-term sleep disturbance and suggest that autophagy dysregulation may be involved in brain impairments in the context of sleep disturbances and disorders
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