Abstract
Sleep deprivation (SD) is commonplace in the modern way of life and has a substantial social, medical, and human cost. Sleep deprivation induces cognitive impairment such as loss of executive attention, working memory decline, poor emotion regulation, increased reaction times, and higher cognitive functions are particularly vulnerable to sleep loss. Furthermore, SD is associated with obesity, diabetes, cardiovascular diseases, cancer, and a vast majority of psychiatric and neurodegenerative disorders are accompanied by sleep disturbances. Despite the widespread scientific interest in the effect of sleep loss on synaptic function, there is a lack of investigation focusing on synaptic transmission on the proteome level. In the present study, we report the effects of SD and recovery period (RP) on the cortical synaptic proteome in rats. Synaptosomes were isolated after 8 h of SD performed by gentle handling and after 16 h of RP. The purity of synaptosome fraction was validated with western blot and electron microscopy, and the protein abundance alterations were analyzed by mass spectrometry. We observed that SD and RP have a wide impact on neurotransmitter-related proteins at both the presynaptic and postsynaptic membranes. The abundance of synaptic proteins has changed to a greater extent in consequence of SD than during RP: we identified 78 proteins with altered abundance after SD and 39 proteins after the course of RP. Levels of most of the altered proteins were upregulated during SD, while RP showed the opposite tendency, and three proteins (Gabbr1, Anks1b, and Decr1) showed abundance changes with opposite direction after SD and RP. The functional cluster analysis revealed that a majority of the altered proteins is related to signal transduction and regulation, synaptic transmission and synaptic assembly, protein and ion transport, and lipid and fatty acid metabolism, while the interaction network analysis revealed several connections between the significantly altered proteins and the molecular processes of synaptic plasticity or sleep. Our proteomic data implies suppression of SNARE-mediated synaptic vesicle exocytosis and impaired endocytic processes after sleep deprivation. Both SD and RP altered GABA neurotransmission and affected protein synthesis, several regulatory processes and signaling pathways, energy homeostatic processes, and metabolic pathways.
Highlights
Sleep is a general phenomenon in animals having neural network and occurs in all of the species investigated; its core function remains controversial
We report the effects of sleep deprivation and recovery period on the rat cortical synaptic proteome
The abundance of synaptic proteins has changed to a greater extent in consequence of Sleep deprivation (SD) than during recovery period (RP), and the levels of most of the altered proteins were upregulated during SD, while RP showed the opposite tendency
Summary
Sleep is a general phenomenon in animals having neural network and occurs in all of the species investigated; its core function remains controversial. Sleep contributes to maintain physiological brain functions such as memory formation and storage and normal cognitive processes as decision-making, language, and categorization and restores performance, while it serves multiple supplementary functions, e.g., affecting the immune system during infectious diseases and reducing calorie use enabling the restoration of depleted energy stores, and it exerts a glymphatic function aimed to remove toxic substances [1,2,3,4,5]. Fluctuations of calcium levels in activated synapses activate multiple calcium-dependent kinases with a role in memory formation resulting in a pretranscriptional amplification of synaptic changes during SWS, which will be transcriptionally stored during REM sleep through CREB-dependent gene expression, triggering plasticity-related protein synthesis [13]. Sleep restores the capacity of learning and actively enhances memory encoding via influencing synaptic plasticity bidirectionally, promoting synaptic up- and downscaling simultaneously in distinct neuronal networks [14]
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