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The mitochondrial proteomic changes of rat hippocampus induced by 28-day simulated microgravity
Guohua Ji1, Hui Chang2, Mingsi Yang2
1State Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing, China.
Abstract:
A large number of aerospace practices have confirmed that the aerospace microgravity environment can lead to cognitive function decline. Mitochondria are the most important energy metabolism organelles, and some studies demonstrate that the areospace microgravity environment can cause mitochondrial dysfunction. However, the relationships between cognitive function decline and mitochondrial dysfunction in the microgravity environment have not been elucidated. In this study, we simulated the microgravity environment in the Sprague-Dawley (SD) rats by -30° tail suspension for 28 days. We then investigated the changes of mitochondrial morphology and proteomics in the hippocampus. The electron microscopy results showed that the 28-day tail suspension increased the mitochondria number and size of rat hippocampal neuronal soma. Using TMT-based proteomics analysis, we identified 163 differentially expressed proteins (DEPs) between tail suspension and control samples, and among them, 128 proteins were upregulated and 35 proteins were downregulated. Functional and network analyses of the DEPs indicated that several of mitochondrial metabolic processes including the tricarboxylic acid (TCA) cycle were altered by simulating microgravity (SM). We verified 3 upregulated proteins, aconitate hydratase (ACO2), dihydrolipoamide S-succinyltransferase (DLST), and citrate synthase (CS), in the TCA cycle process by western blotting and confirmed their differential expressions between tail suspension and control samples. Taken together, our results demonstrate that 28-day tail suspension can cause changes in the morphology and metabolic function of hippocampus mitochondria, which might represent a mechanism of cognitive disorder caused by aerospace microgravity.
Insights
Spaceflight microgravity impacts brain function. Simulated microgravity in rats altered hippocampal mitochondria morphology and metabolism, potentially explaining cognitive decline during space missions.
Area of Science:
- Neuroscience
- Space Biology
- Mitochondrial Biology
Background:
- Aerospace microgravity is linked to cognitive decline.
- Microgravity may induce mitochondrial dysfunction.
- The link between cognitive changes and mitochondrial issues in microgravity remains unclear.
Purpose of the Study:
- To investigate the effects of simulated microgravity on hippocampal mitochondrial morphology and proteomics.
- To elucidate the relationship between microgravity-induced mitochondrial changes and cognitive function decline.
Main Methods:
- Simulated microgravity using -30° tail suspension in Sprague-Dawley rats for 28 days.
- Electron microscopy to assess mitochondrial morphology.
- TMT-based proteomics to identify differentially expressed proteins (DEPs) in the hippocampus.
- Western blotting to validate key protein changes.
Main Results:
- Tail suspension increased mitochondria number and size in hippocampal neurons.
- 163 DEPs were identified, with 128 upregulated and 35 downregulated.
- Simulated microgravity altered mitochondrial metabolic processes, including the tricarboxylic acid (TCA) cycle.
- Key TCA cycle proteins (ACO2, DLST, CS) were upregulated.
Conclusions:
- 28-day tail suspension alters hippocampal mitochondria morphology and metabolic function.
- These mitochondrial changes may underlie cognitive disorders associated with aerospace microgravity.
- Further research is needed to fully understand the mechanisms linking microgravity, mitochondrial dysfunction, and cognitive impairment.
