iTRAQ-based proteomics analysis of hippocampus in spatial memory deficiency rats induced by simulated microgravity.

It has been demonstrated that simulated microgravity (SM) may lead to cognitive dysfunction. However, the underlying mechanism remains unclear. In present study, tail-suspension (30°) rat was employed to explore the effects of 28 days of SM on hippocampus-dependent learning and memory capability and the underlying mechanisms. We found that 28-day tail-suspension rats displayed decline of learning and memory ability in Morris water maze (MWM) test. Using iTRAQ-based proteomics analysis, a total of 4774 proteins were quantified in hippocampus. Of these identified proteins, 147 proteins were differentially expressed between tail-suspension and control group. Further analysis showed these differentially expressed proteins (DEPs) involved in different molecular function categories, and participated in many biological processes. Based on the results of PANTHER pathway analysis and further western blot verification, we observed the expression of glutamate receptor 1 (GluR1) and glutamate receptor 4 (GluR4) which involved in metabotropic glutamate receptor group III pathway and ionotropic glutamate receptor pathway were significantly induced by SM. Moreover, an increased concentration of glutamic acid (Glu) was also found in hippocampus while the concentrations of 5-hydroxytryptamine (5-HT), dopamine (DA), γ-amino acid butyric acid (GABA) and epinephrine (E) were decreased. Our finding confirms that 28-day SM exposure can cause degrading of the spatial learning and memory capability and the possible mechanisms might be related with glutamate excitotoxicity and imbalances in specific neurotransmitters. BIOLOGICAL SIGNIFICANCE: The goal of sending astronauts farther into space and extending the duration of spaceflight missions from months to years will challenge the current capabilities of bioastronautics. The investigation of the physiological and pathological changes induced by spaceflight will be critical in developing countermeasures to ensure astronauts to complete spaceflight mission accurately and effectively and return to earth safely. It has been demonstrated that spaceflight may lead to impairments in cognitive function which is crucial for mission success. Here we show that long-term simulated microgravity, the most potent environment risk factor during spaceflight, impairs the spatial learning and memory of rats and the underlying mechanism may be involved in glutamate excitotoxicity and imbalances in specific neurotransmitters release in hippocampus, which may provide new insight for the countermeasures of cognitive impairment during spaceflight.