Characterization of gene expression profiles in the mouse brain after 35 days of spaceflight mission

Abstract

It has been proposed that neuroinflammatory response plays an important role in the neurovascular remodeling in the brain after stress. The goal of the present study was to characterize changes in the gene expression profiles associated with neuroinflammation, neuronal function, metabolism and stress in mouse brain tissue. Ten-week old male C57BL/6 mice were launched to the International Space Station (ISS) on SpaceX-12 for a 35-day mission. Within 38 ± 4 h of splashdown, mice were returned to Earth alive. Brain tissues were collected for analysis. A novel digital color-coded barcode counting technology (NanoString^TM) was used to evaluate gene expression profiles in the spaceflight mouse brain. A set of 54 differently expressed genes (p < 0.05) significantly segregates the habitat ground control (GC) group from flight (FLT) group. Many pathways associated with cellular stress, inflammation, apoptosis, and metabolism were significantly altered by flight conditions. A decrease in the expression of genes important for oligodendrocyte differentiation and myelin sheath maintenance was observed. Moreover, mRNA expression of many genes related to anti-viral signaling, reactive oxygen species (ROS) generation, and bacterial immune response were significantly downregulated. Here we report that significantly altered immune reactions may be closely associated with spaceflight-induced stress responses and have an impact on the neuronal function.

Fig. 1. Spaceflight-induced changes of gene expression related to neuronal function.

Bar graph summarizing log2 fold-changes of significantly differentially expressed genes (DEG) (p < 0.05) in the flight (FLT) group compared to the ground control (GC) group in genes directly related to neuronal function. N = 6/group. p values are calculated using one-way analysis of variance (ANOVA) and Tukey’s HSD (honestly significant difference) test. Source data are provided as a Source Data file.

Fig. 2. Spaceflight-induced changes of gene expression related to neuronal support cell function.

Bar graph summarizing log2 fold-changes of significantly differentially expressed genes (DEG) (p < 0.05) in the flight (FLT) group compared to the ground control (GC) group in genes directly related to neuronal supporting cell function. N = 6/group. P values are calculated using one-way analysis of variance (ANOVA) and Tukey’s HSD (honestly significant difference) test. Source data are provided as a Source Data file.

Fig. 3. Spaceflight-induced changes of gene expression related to immune function and inflammation.

Bar graph summarizing log2 fold-changes of significantly differentially expressed genes (DEG) (p < 0.05) in the flight (FLT) group compared to the ground control (GC) group in genes directly related to immune function and inflammation. N = 6/group. p values are calculated using one-way analysis of variance (ANOVA) and Tukey’s HSD (honestly significant difference) test. Source data are provided as a Source Data file.

Fig. 4. Spaceflight-induced changes of gene expression related to cellular stress and growth function.

Bar graph summarizing log2 fold-changes of significantly differentially expressed genes (DEG) (p < 0.05) in the flight (FLT) group relative to the ground control (GC) group in genes directly related to cellular stress and growth function. N = 6/group. p values are calculated using one-way analysis of variance (ANOVA) and Tukey’s HSD (honestly significant difference) test. Source data are provided as a Source Data file.

Fig. 5. Spaceflight-induced changes of pathway scores.

Summarized pathway scores in flight (FLT) group vs. ground control (GC). *Significantly upregulated pathways (p < 0.05), include: cytokine signaling, Angiogenesis, Epigenetic regulation, and Notch. **Significantly (p < 0.05) or strong trend (p = 0.07) downregulated pathways, include: Oligodendrocyte function, Innate immune response, and Microglia function. p values are by one-way ANOVA and Tukey’s post hoc test. Source data are provided as a Source Data file.

Fig. 6. Spaceflight-induced changes in nueroinflammation pathway scores among flight (FLT) and ground controls (GC) groups.

Boxplots depict pathway scores on the y-axis and the experimental conditions on the x-axis. N = 5–6 /group. p values are calculated using one-way analysis of variance (ANOVA) and Tukey’s HSD (honestly significant difference) test. a Oligodendrocyte function score p < 0.05, b cytokine signaling score p < 0.05, c innate immune response score p < 0.05, d angiogenesis score p < 0.05, e epigenetic regulation score p < 0.05, f notch score p < 0.01, and g Microglia function score p = 0.07. Boxes are the range between first (25%) and the third (75%) quartile, the center line is the median, the whiskers include the variability those quartiles. Source data are provided as a Source Data file.