0058 Effects of Acute Total Sleep Deprivation on Human Plasma N-glycans

Abstract

Abstract Introduction There is a need for a novel biomarker that can be used to measure sleep sufficiency as it pertains to fitness for duty. As glycans (polysaccharides) are known to be involved in modifying protein effectiveness, we are exploring these as biomarkers that may be sensitive to differences between sleep deprivation and normal healthy adult sleep duration. We have measured one major class of glycans, called N-glycans, which are covalently linked to asparagine residues of polypeptide chains of membrane-bound and secreted proteins. We compared the plasma N-glycan profiles of participants before and after they participated in a total sleep deprivation protocol. Methods 10 healthy participants (6 male, 4 female) aged 30–44 went through 88 hours of total sleep deprivation. Hourly blood draws were taken via forearm catheter throughout the protocol. N-glycan analysis was performed using plasma samples collected at 17:35 prior to the first night of sleep deprivation and at 17:35 following 82.5 hours of continuous wakefulness. N-glycans were first cleaved from peptides and isolated from plasma, and profiles were then measured using Matrix-Assisted Laser Desorption/Ionization-Time of Flight (MALDI-TOF) mass spectrometry. Results 66 N-glycans were observed in our profiles. Of these, the relative abundance of 17 N-glycans were significantly different following sleep deprivation (paired t-test, 13 with p<0.05, 4 with p<0.01). In each case, the relative abundance was lower in the sleep deprivation time point. We found two structures, Hex6HexNAc5NeuAc3 and Hex7HexNAc6NeuAc2, which were also significant in one of our previous chronic sleep restriction protocols. Conclusion While we observed that many N-glycans decreased in relative abundance, it is unclear whether these changes represent a shift in glycan synthesis or result from decreased expression of the proteins they are bound to. Our next steps involve exploring the functions of the proteins associated with Hex6HexNAc5NeuAc3 and Hex7HexNAc6NeuAc2, and measuring their expression levels. Support NIH/HL75501; NIH/National Center for Research Resources UL1-RR02758 and M01-RR01032 to the Harvard Clinical and Translational Science Center.