Quantitative proteomic analysis of cortex in the depressive-like behavior of rats induced by the simulated complex space environment

Long-term spaceflight has always been challenging for astronauts due to the extremely complicated space environmental conditions, including microgravity, noise, confinement, and circadian rhythms disorders, which may cause adverse effects on astronauts' mental health, such as anxiety and depression. Unfortunately, so far, the underlying mechanism is not fully understood. Hence, a novel type of box and rat cage was designed and built in order to simulate complex space environment on the ground. After earth-based simulation for 21 days, the rats exhibited the depressive-like behavior according to the sucrose preference and forced swimming test. We applied label-free quantitative proteomics to explore the molecular mechanisms of depressive-like behavior through global changes in cortical protein abundance, given that the cortex is the hub of emotional management. The results revealed up-regulated spliceosome proteins in contrast to down-regulated oxidative phosphorylation (OXPHOS), glutamatergic, and GABAergic synapse related proteins in the simulated complex space environment (SCSE) group. Furthermore, PSD-95 protein was found down-regulated in mass spectrometry, reflecting its role in the psychopathology of depression, which was further validated by Western blotting. These findings provide valuable information to better understand the mechanisms of depressive-like behavior. Significance: Quantitative proteomic analysis can quantify differentially abundant proteins related to a variety of potential signaling pathways in the rat cortex in the simulated complex space environment. These findings not only provide valuable information to better understand the mechanisms of depressive-like behavior, but also might offer the potential targets and develop countermeasures for the mental disorders to maintain the health of astronauts during the long-term spaceflight.