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

ABSTRACT

BACKGROUND: Sleep is a physiological event that directly influences health by affecting the immune system, in which calcium (Ca(2+)) plays a critical signaling role. We performed live cell measurements of cytosolic Ca(2+) mobilization to understand the changes in Ca(2+) 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 72h) and Ca(2+) intracellular fluctuations were evaluated in splenocytes by confocal microscopy. We also performed spleen cell evaluation by flow cytometry and analyzed intracellular Ca(2+) mobilization in endoplasmic reticulum and mitochondria. Additionally, Ca(2+) channel gene expression was evaluated RESULTS: Splenocytes showed a progressive loss of intracellular Ca(2+) maintenance from endoplasmic reticulum (ER) stores. Transient Ca(2+) 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) Ca(2+) channels. CONCLUSIONS AND GENERAL SIGNIFICANCE: These novel data suggest that SD impairs Ca(2+) signaling, most likely as a result of ER stress, leading to an insufficient Ca(2+) 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.