Deep Membrane Proteome Profiling of Rat Hippocampus in Simulated Complex Space Environment by SWATH

Despite the development and great progress in the field of space biology, the astronauts are still facing many challenges in space. The space environment in which astronauts stay includes microgravity, noise, circadian rhythms disorder, and confinement, which has deep effect both on the physiology and psychology of astronauts. It was reported that long-term flight could cause the astronauts’ anxiety and depression. However, the underlying mechanism is not yet fully understood. Therefore, in the present study, the rat tail suspension model with noise, circadian rhythms, and confinement was employed to simulate complex space environment. We found that the rats exhibited the depressive-like behavior by the sucrose preference, forced swimming, and open-field tests. The membrane proteome of the rat hippocampus was investigated by “SWATH quantitation” technology both in control and simulated complex space environment (SCSE) groups. Out of 4520 quantified proteins, 244 differentially expressed membrane proteins were obtained between the SCSE and control rats, which were functionally enriched in a series of biological processes, such as translation, protein phosphorylation, brain development, endocytosis, nervous system development, axonogenesis, and vesicle-mediated transport. We found a reduction level of neurexin-2, the light, medium, heavy polypeptide of neurofilament, rab 18, synaptogyrin 1, and syntaxin-1A and an increase level of neuroligin-1, munc18, snapin, synaptotagmin XII, complexin-1, etc., which may play a key part in the development of depression. Furthermore, GSK-3β protein was upregulated in mass spectrometry, which was further validated by western blotting. The results of the study do the favor in designing the effective countermeasures for the astronauts in the future long-term spaceflight.