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

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 imm...

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Detalles Bibliográficos
Autores: Lungato, Lisandro [UNIFESP], Gazarini, Marcos Leoni [UNIFESP], Paredes-Gamero, Edgar Julian [UNIFESP], Tersariol, Ivarne Luis dos Santos [UNIFESP], Tufik, Sergio [UNIFESP], D'Almeida, Vania [UNIFESP]
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2012
País:Brasil
Institución:Universidade Federal de São Paulo (UNIFESP)
Repositorio:Repositório Institucional da UNIFESP
Idioma:inglés
OAI Identifier:oai:repositorio.unifesp.br:11600/35515
Acceso en línea:http://dx.doi.org/10.1016/j.bbagen.2012.09.010
http://repositorio.unifesp.br/handle/11600/35515
Access Level:acceso abierto
Palabra clave:Ca2+ signaling
Splenocytes
Sleep deprivation
Mitochondrial dysfunction
Mice
Descripción
Sumario: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.