Sleep Deprivation Influences Circadian Gene Expression in the Lateral Habenula.

Beilin Zhang,Jing Yang,Yang Li,Yanxia Gao,Hua Zhao

doi:10.1155/2016/7919534

Beilin Zhang, Jing Yang + Show 3 more

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https://doi.org/10.1155/2016/7919534

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Abstract

Sleep is governed by homeostasis and the circadian clock. Clock genes play an important role in the generation and maintenance of circadian rhythms but are also involved in regulating sleep homeostasis. The lateral habenular nucleus (LHb) has been implicated in sleep-wake regulation, since LHb gene expression demonstrates circadian oscillation characteristics. This study focuses on the participation of LHb clock genes in regulating sleep homeostasis, as the nature of their involvement is unclear. In this study, we observed changes in sleep pattern following sleep deprivation in LHb-lesioned rats using EEG recording techniques. And then the changes of clock gene expression (Per1, Per2, and Bmal1) in the LHb after 6 hours of sleep deprivation were detected by using real-time quantitative PCR (qPCR). We found that sleep deprivation increased the length of Non-Rapid Eye Movement Sleep (NREMS) and decreased wakefulness. LHb-lesioning decreased the amplitude of reduced wake time and increased NREMS following sleep deprivation in rats. qPCR results demonstrated that Per2 expression was elevated after sleep deprivation, while the other two genes were unaffected. Following sleep recovery, Per2 expression was comparable to the control group. This study provides the basis for further research on the role of LHb Per2 gene in the regulation of sleep homeostasis.

Highlights

Clock genes are a class of molecules essential for the generation and maintenance of circadian rhythms
We compared the difference between sleep and wake cycle following 6 h sleep deprivation before and after lateral habenular nucleus (LHb) lesions in the same group rats to determine the effect of LHb lesions on the sleep rebound induced by a 6 h sleep deprivation
Further analysis demonstrated that the duration of wakefulness following the sleep deprivation was longer after LHb lesion than before LHb lesion (540.44 ± 66.91 min versus 461.14 ± 44.46 min, t = 5.787, df = 5, P = 0.0022, Figure 2(b)(B1)) and Non-Rapid Eye Movement Sleep (NREMS) was shorter after LHb lesion than before LHb lesion (439.69± 31.29 min versus 493.14 ± 51.07 min, t = 4.335, df = 5, P = 0.0075, Figure 2(c)(C1))

Summary

Introduction

Clock genes are a class of molecules essential for the generation and maintenance of circadian rhythms. The protein products of clock genes collaborate to establish a network of autoregulatory feedback loops. Such loops are thought to be exclusively involved in the maintenance of a ∼24 h oscillation cycle and the regulation of physiological functions. The core loop includes a brain and muscle ARNT-like protein 1/circadian locomotor output cycles kaput (Bmal1/clock) heterodimer that binds to Enhancer Box (E-box) containing elements on the promoters of the core clock genes, period (Per, Per, Per3), and cryptochrome (Cry, Cry2) [1, 2]. Transgenic clock gene-deficient mice demonstrate robust circadian rhythms when compared to wild-type animals [8]

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