Leukocyte Expression of Type 1 and Type 2 Purinergic Receptors and Pro-Inflammatory Cytokines during Total Sleep Deprivation and/or Sleep Extension in Healthy Subjects

• Published in: Frontiers in neuroscience 2017-05, Vol.11, p.240-240
• Main Authors: Chennaoui, Mounir, Arnal, Pierrick J, Drogou, Catherine, Leger, Damien, Sauvet, Fabien, Gomez-Merino, Danielle
• Format: Article
• Language: English
• Subjects: A1 gene; Adenosine; Adenosine A2A receptors; adenosine and purinergic receptors; Adenosine triphosphate; Brain research; Cytokines; Eye movements; Gene expression; IL-1β; Inflammation; Latency; Leukocytes; Metabolism; Metabolites; Neurons; Neuroscience; Neurosciences; Purine receptors; Sleep and wakefulness; Sleep deprivation; Tumor necrosis factor-α
• ISSN: 1662-4548; 1662-453X; 1662-453X
• DOI: 10.3389/fnins.2017.00240

The purinergic type P1 (adenosine A and A ) receptors and the type P2 (X7) receptor have been suggested to mediate physiological effects of adenosine and adenosine triphosphate on sleep. We aimed to determine gene expression of A R (receptor), A R, and P2RX in leukocytes of healthy subjects during total sleep deprivation followed by sleep recovery. Expression of the pro-inflammatory cytokines IL-1β and TNF-α were also determined as they have been characterized as sleep regulatory substances, via P2RX activation. Blood sampling was performed on 14 young men (aged 31.9 ± 3.9) at baseline (B), after 24 h of sleep deprivation (24 h- ), and after one night of sleep recovery (R). We compared gene expression levels after six nights of habitual (22.30-07.00) or extended (21.00-07.00) bedtimes. Using quantitative real-time PCR, the amount of mRNA for A R, A R, P2RX , TNF-α, and IL-1β was analyzed. After 24 h- compared to B, whatever prior sleep condition, a significant increase of A R expression was observed that returned to basal level after sleep recovery [day main effect, = 10.8, < 0.001]. In both sleep condition, a day main effect on P2RX mRNA was observed [ = 6.7, = 0.005] with significant increases after R compared with 24 h- . TNF-α and IL-1β expressions were not significantly altered. Before 24 h- (baseline), the A R expression was negatively correlated with the latency of stage 3 sleep during the previous night, while that of the A R positively. This was not observed after sleep recovery following 24 h- . This is the first study showing increased A R and not A gene expression after 24 h- in leukocytes of healthy subjects, and this even if bedtime was initially increased by 1.5 h per night for six nights. In conclusion, prolonged wakefulness induced an up-regulation of the A2A receptor gene expression in leukocytes from healthy subjects. Significant correlations between baseline expression of A and A receptors in peripheral cells and stage 3 sleep suggested their involvement in mediating the effects of adenosine on sleep.