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Effect of sleep deprivation and sleep rebound on the expression of molecules involved in homeostatic sleep regulation

Grant number: 17/18455-5
Support type:Scholarships in Brazil - Master
Effective date (Start): January 01, 2018
Effective date (End): October 31, 2019
Field of knowledge:Biological Sciences - Physiology
Principal Investigator:Monica Levy Andersen
Grantee:Guilherme Luiz Fernandes
Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Sleep homeostasis is controled by several sleep regulatory substances (SRS), such as interleukin-1b (IL-1b) and tumoral necrosis factor a (TNF a). However, how those SRS act is still discussed. The local sleep hypothesis develops the concept that small neuronal networks exhibit states similar to sleep-wake cycle and collectively, might influence organism behavior. Its regulation involves the SRSs, ATP and its receptor P2X7 and neuronal sensibilization via receptors such as AMPAR. Nevertheless, there is a lack of evidence which relates sleep pressure to the homeostatic sleep regulation mechanisms presented, which are testable by means of acute sleep deprivation. This lack of evidence also exists in relation to this mechanism in chronic sleep loss. Therefore, the temporal relationship of IL-1b, TNFa, nuclear factor kB (NF-kB), the receptors P2X7 and AMPAR, in the context of homeostatic sleep regulation in different brain regions will be investigated. 100 C57BL/6J mice, distributed in 5 groups of sleep deprivation, 5 groups of sleep rebound and respective control groups will be used. The mice will undergo sleep deprivation by gentle handling method for 3, 6, 9 or 12 hours and the last group will be sleep deprived for 6 hours over 5 consecutive days. Sleep rebound mice will undergo similar sleep deprivation protocols, but opportunity for sleeping for 1, 2, 3, 4 hours or 1 day will be given, respectively. At the end of experimental protocols, mice will be euthanized, and brain tissue will be collected for posterior protein analysis of IL-1b, TNFa, NF-kB, P2X7 and AMPAR. It is hoped that this study allows to observe correlations between time of extended wakefulness and the studied molecules, so that homeostatic sleep regulatory mechanisms might be elucidated. (AU)

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