Spaceflight-induced gene expression profiles in the mouse brain are attenuated by treatment with the antioxidant BuOE
The demands of deep-space pose a health risk to the central nervous system that has long been a concern when sending humans to space. While little is known about how spaceflight affects transcription spatially in the brain, understanding this has the potential to aid strategies that mitigate the effects of spaceflight on the brain. Therefore, we performed GeoMx Digital Spatial Profiling of mouse brains subjected to either space flight, or grounded controls. Four brain regions were selected: Cortex, Frontal Cortex, Corunu Ammonis I, and Dentate Gyrus. Antioxidants have emerged as a potential means of attenuating the effects of spaceflight, so we treated a subset of the mice with a superoxide dismutase mimic, MnTnBuOE-2-PyP 5+ (BuOE). Our analysis revealed hundreds of differentially expressed genes due to spaceflight in each of the four brain regions. Both common and region-specific transcriptomic responses were observed. Pathways sensitive to oxidative stress, and metabolic pathways, were enriched in the four brain regions due to spaceflight. These findings enhance our understanding of brain regional variation in susceptibility to spaceflight conditions. BuOE reduced the transcriptomic effects of spaceflight at a large number of genes, suggesting that this compound may attenuate oxidative stress-induced brain damage by the spaceflight environment. Overall design: Ten-week-old C57BL/6 male mice were launched at the Kennedy Space Center (KSC) and spent 35 days aboard the international space station (ISS). All mice were maintained at an ambient temperature of 26–28?°C with a 12-hour light/dark cycle during the flight. All mice were provided NASA Nutrient-upgraded Rodent Food Bar (NuRFB) and autoclaved deionized water ad libitum. MnTnBuOE-2-PyP5+ (BuOE) at 1 mg/kg (0.2 mL) was administrated subcutaneously 7 days prior to the flight launch and weekly aboard the ISS. All mice were subdivided into saline or BuOE treated groups. Upon return to the Earth, spaceflight mice were transported to the research laboratory at Roskamp Institute, Sarasota, Florida within 20?hours of splashdown. Mice were exsanguinated by closed-cardiac blood collection under deep Ketamine/Xylazine (150/45 mg/kg) anesthesia, followed by cervical dislocation as a secondary euthanasia method to ensure death. Ground control mice were maintained on Earth for 35 days in flight hardware cages under similar environmental conditions as the flight groups, including the same food, light/dark, temperature, treatment (SAL or BuOE), and euthanasia regimens. The protocol for GC mice commenced three days subsequent to the commencement of the protocol for spaceflight mice.