Identification and Characterization of Molecular Inhibitors of Cognitive Performance

We will use Proteinchip© Arrays/SELDI-TOF-MS (Ciphergen) to obtain a large-scale profiling of the brain proteins affected by sleep loss. Fruit flies, rats and sparrows will be sleep recorded and sleep deprived in the laboratory of Dr. Chiara Cirelli (UW–Madison). Rats will be studied after acute and chronic sleep deprivation and sleep restriction. Wild-type flies and sleep-deprivation resistant mutant flies will be studied. Sparrows will be studied when migrating (when they are not cognitively impaired) and during the non-migratory season (when they are, if sleep deprived). Phase I demonstrated that it is possible, using these animal models, to identify potential biomarkers of cognitive performance. Phase II will validate and extend these results by studying fractionated samples in a larger number of animals. We will use univariate/multivariate statistical analysis to discover multi-component biomarker patterns, and will identify up to 30 protein peaks. These findings will be instrumental 1) to identify molecular correlates of performance in individual sleep deprived subjects; 2) to search for biomarkers of sleep loss in peripheral tissues; 3) to design a diagnostic protein array that can distinguish sleep deprived subjects from controls; 4) to design a diagnostic protein array that can predict an individual’s performance under conditions of sleep deprivation.