Sleep deprivation impairs calcium signaling in mouse splenocytes and leads to a decreased immune response

Sleep deprivation impairs calcium signaling in mouse splenocytes and leads to a decreased immune response

Author Lungato, Lisandro Autor UNIFESP Google Scholar
Gazarini, Marcos Leoni Autor UNIFESP Google Scholar
Paredes-Gamero, Edgar Julian Autor UNIFESP Google Scholar
Tersariol, Ivarne Luis dos Santos Autor UNIFESP Google Scholar
Tufik, Sergio Autor UNIFESP Google Scholar
D'Almeida, Vania Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Abstract Background: Sleep is a physiological event that directly influences health by affecting the immune system, in which calcium (Ca2+) plays a critical signaling role. We performed live cell measurements of cytosolic Ca2+ mobilization to understand the changes in Ca2+ signaling that occur in splenic immune cells after various periods of sleep deprivation (SD).Methods: Adult male mice were subjected to sleep deprivation by platform technique for different periods (from 12 to 72 h) and Ca2+ intracellular fluctuations were evaluated in splenocytes by confocal microscopy. We also performed spleen cell evaluation by flow cytometry and analyzed intracellular Ca2+ mobilization in endoplasmic reticulum and mitochondria. Additionally. Ca2+ channel gene expression was evaluatedResults: Splenocytes showed a progressive loss of intracellular Ca2+ maintenance from endoplasmic reticulum (ER) stores. Transient Ca2+ buffering by the mitochondria was further compromised. These findings were confirmed by changes in mitochondrial integrity and in the performance of the store operated calcium entry (SOCE) and stromal interaction molecule 1 (STIM1) Ca2+ channels.Conclusions and general significance: These novel data suggest that SD impairs Ca2+ signaling, most likely as a result of ER stress, leading to an insufficient Ca2+ supply for signaling events. Our results support the previously described immunosuppressive effects of sleep loss and provide additional information on the cellular and molecular mechanisms involved in sleep function. (C) 2012 Elsevier B.V. All rights reserved.
Keywords Ca2+ signaling
Sleep deprivation
Mitochondrial dysfunction
Language English
Sponsor AFIP (Associacao Fundo de Incentivo a Pesquisa)
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Grant number FAPESP: 05/04366-3
FAPESP: CEPID 98/14303-6
Date 2012-12-01
Published in Biochimica Et Biophysica Acta-general Subjects. Amsterdam: Elsevier B.V., v. 1820, n. 12, p. 1997-2006, 2012.
ISSN 0304-4165 (Sherpa/Romeo, impact factor)
Publisher Elsevier B.V.
Extent 1997-2006
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000311004000018

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