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

• Published in: Biochimica et biophysica acta Vol. 1820; no. 12; pp. 1997 - 2006
• Main Authors: Lungato, Lisandro, Gazarini, Marcos L., Paredes-Gamero, Edgar J., Tersariol, Ivarne l.S., Tufik, Sergio, D'Almeida, Vânia
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.12.2012
• Subjects: adults; Animals; Ca2 + signaling; calcium; Calcium - metabolism; calcium channels; calcium signaling; Calcium Signaling - physiology; confocal microscopy; endoplasmic reticulum; Endoplasmic Reticulum - metabolism; flow cytometry; gene expression; immune response; Lysosomes - metabolism; Male; males; Membrane Potential, Mitochondrial; Membrane Proteins - genetics; Membrane Proteins - metabolism; Mice; mitochondria; Mitochondria - immunology; Mitochondria - metabolism; Mitochondrial dysfunction; Neoplasm Proteins - genetics; Neoplasm Proteins - metabolism; sleep; Sleep deprivation; Sleep Deprivation - immunology; Sleep Deprivation - metabolism; Sleep Deprivation - pathology; spleen; Spleen - cytology; Spleen - immunology; Spleen - metabolism; Splenocytes; Stromal Interaction Molecule 1; Mice; Mitochondrial dysfunction; Ca2+ signaling; Splenocytes; Sleep deprivation
• ISSN: 0304-4165; 0006-3002; 1872-8006
• DOI: 10.1016/j.bbagen.2012.09.010

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). Adult male mice were subjected to sleep deprivation by platform technique for different periods (from 12 to 72h) 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 evaluated 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. 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. ► Sleep deprivation impairs calcium signaling in mice splenocytes. ► Sleep deprivation results in decrease in calcium stores in endoplasmic reticulum. ► Mitochondrial membrane potential in splenocytes is lost after sleep deprivation. ► Sleep deprivation results in splenocytes lysosomal integrity leakage. ► STIM expression is augmented after sleep deprivation in mice spleen.