Transcriptome sequencing reveals the promotion of apoptosis and M1 polarization of microglia under simulated microgravity

The exponential progress in the field of space science and technology has facilitated the prolonged habitation of astronauts in the space environment. However, the neurological and cognitive impairments of astronauts have become major factor that directly impede the successful completion of space missions. Studies have demonstrated that microgravity can diminish neuronal functions and cognitive abilities by altering the microenvironment of the brain (BME). Microglia, vital immune cells responsible for regulating the integrity of the blood-brain barrier, have been identified as the principal contributing elements to the neurological deterioration observed in microgravity conditions. The primary objective of this study was to provide an understanding of the molecular processes underlying the behavior of microglia under conditions of microgravity. Using a Random Positioning Machine (RPM) to simulate microgravity, our study found that microgravity reduces BV2 microglial cell viability, induces M1 polarization, and significantly increases late apoptosis. Transcriptome analysis revealed 142 differentially expressed genes related to microglial phenotype and inflammation, with qPCR validating selected DEGs. These results elucidate the molecular mechanisms of microglial behavior under microgravity, highlighting gene expression changes and cellular damage. This study provides a conceptual framework for comprehending the influence of microgravity on the neurological system, establishing countermeasures against functional damage to the nervous system caused by space flight, and serving as a reference for future deep space exploration and long-term manned space medical support.