Sleep Deprivation Induces Neuroinflammation and Depressive-like Behaviors by Impairing the Regulation of Circadian Clock Genes Expression in Rats

Abstract

Background: Sleep loss leads to a spectrum of mood disorders such as anxiety, cognitive dysfunction and motor coordination impairment in many individuals. However, the underlying mechanisms are largely unknown. Methods: In this study, we examined the effects of sleep deprivation (SD) on depression and the mechanism by subjecting rats to a slowly rotating platform for 3 days to mimic the process of sleep loss. Sleep-deprived animals were tested behaviorally for anxiety- and depressive-like behaviors. We further studied the effects of SD on hypothalamic-pituitary-adrenal (HPA) axis activity, and at the end of the experiment, brains were collected to measure the circadian clock genes expression in the hypothalamus, glial cell activation and inflammatory cytokine alterations. Results: Our results indicated that SD for 3 days resulted in anxiety- and depressive-like behaviors. SD exaggerated cortisol response to HPA axis, significantly altered the mRNA profile of circadian clock genes, and induced neuroinflammation by increasing the expression of glial cell markers, including the microglial marker ionized calcium-binding adapter molecule 1 (Iba1) and the astroglial marker glial fibrillary acidic protein (GFAP). The expression of M1 and M2 microglial markers (Arg-1 and CD206, respectively) and pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α) were increased in the brain. Conclusion: These results indicated that SD for 3 days induced anxiety- and depression-like behaviors in rats by impairing the regulation of circadian clock genes and inducing neuroinflammation, ultimately resulting in brain injury.

Impact of Sleep on Autophagy and Neurodegenerative Disease: Sleeping Your Mind Clear

“…These cytokines stimulate nonrestorative NREM sleep indicating a relationship between sleep and proinflammatory response together [139,140]. Recently, sleep deprivation in rats was demonstrated to directly cause neuroinflammation [141]. Interestingly, this study also showed an increase in AQP4 in sleep deprived rats.…”