Proteomic Analysis of Rat Serum Revealed the Effects of Chronic Sleep Deprivation on Metabolic, Cardiovascular and Nervous System

Abstract Sleep is an essential and fundamental physiological process that plays crucial roles in the balance of psychological and physical health. Sleep disorder may lead to adverse health outcomes. The effects of sleep deprivation were extensively studied, but its mechanism is still not fully understood. The present study aimed to identify the alterations of serum proteins associated with chronic sleep deprivation, and to seek for potential biomarkers of sleep disorder mediated diseases. A label-free quantitative proteomics technology was used to survey the global changes of serum proteins between normal rats and chronic sleep deprivation rats. A total of 309 proteins were detected in the serum samples and among them, 117 proteins showed more than 1.8-folds abundance alterations between the two groups. Functional enrichment and network analyses of the differential proteins revealed a close relationship between chronic sleep deprivation and several biological processes including energy metabolism, cardiovascular function and nervous function. And four proteins including pyruvate kinase M1, clusterin, kininogen1 and profilin-1were identified as potential biomarkers for chronic sleep deprivation. The four candidates were validated via parallel reaction monitoring (PRM) based targeted proteomics. In addition, protein expression alteration of the four proteins was confirmed in myocardium and brain of rat model. In summary, the comprehensive proteomic study revealed the biological impacts of chronic sleep deprivation and discovered several potential biomarkers. This study provides further insight into the pathological and molecular mechanisms underlying sleep disorders at protein level.