Transcriptomic analysis of embryonic mouse hypothalamic N38 cells exposed to high-energy protons and/or simulated microgravity.

Purpose: Space exploration poses unique challenges to astronauts, especially the effects of space radiation and microgravity (μG). Understanding molecular responses to these factors is crucial for ensuring astronaut health, and this study aimed to identify transcriptomic changes in mouse hypothalamic cell line N38 (mHypoE-N38) caused by simulated space environments.

Method: Four experimental groups were established, namely, a ground condition group (GC; the control group), a proton irradiated group (the space radiation group), a simulated μG group, and a proton irradiated × simulated μG group (the combination group). RNA sequencing and quantitative real-time polymerase chain reaction were performed to investigate key altered genes and to validate them.

Results: Three hundred and fifty-five differentially expressed genes were identified. Notably, the expressions of and genes were upregulated in all three experimental groups, suggesting a shared regulatory mechanism with potential consequences for brain function during space missions. Moreover, the study revealed significant alterations in genes belonging to the and families, indicating active response to DNA damage and telomere maintenance. PCR results validated that , family, and families (, , and ) were significantly upregulated at the mRNA level in the combination group, while , , and were not reproduced.

Conclusion: The present study on mHypoE-N38 cells exposed to space environments revealed a complex molecular narrative with disease-oriented implications. The knowledge gained might serve as a cornerstone for developing strategies to mitigate potential health risks associated with extended exposure to space-related stressors.