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Gene responses in mouse brain to long-term exposure to microgravity

ABSTRACT: The spaceflight experiment was carried out using male C57BL/10J mice (8 weeks old at launch). Wild type mice (n=3) were launched by Space Shuttle Discovery and housed on the International Space Station (ISS) for 91 days. They returned to the Earth by Space Shuttle Atlantis. But only one mouse returned to the Earth alive. Whole brain was sampled from the mouse killed by inhalation of carbon dioxide at the Life Sciences Support Facility of Kennedy Space Center within 3-4 hours after landing. After the spaceflight experiment, the on-ground experiment was also carried out at the Advanced Biotechnology Center in Genova, Italy. A mouse with the same species, sex, and age was housed in mice drawer system (MDS), which was utilized for the spaceflight (SF) mice, for 3 months as the ground control (GC). Another mouse was housed in normal vivarium cage as the laboratory control (LC). Amount of food and water supplementation and environmental conditions were simulated as the flight group. After 3 months, brain was sampled from one mouse in group GC and LC, respectively. Comprehensive analyses of gene expression were performed in the right brain. Total of 4,000 genes were analyzed. The expression levels of 60 genes significantly changed in response to SF compared with LC and/or GC. The 15 and 16 genes were up- (> 2 folds) and down-regulated (< 0.5 folds), respectively, following SF vs. GC. The levels of 58 genes were significantly altered by housing in MDS in space and/or on the ground. Forty seven and 11 genes were significantly up- and down-regulated vs. LC. Twenty seven out of these genes responded to caging in MDS both in space and on the ground. Further, 31 genes were influenced by housing in MDS on the Earth.

ORGANISM(S): Mus musculus

PROVIDER: GSE32077 | GEO | 2012/09/13

SECONDARY ACCESSION(S): PRJNA147587

REPOSITORIES: GEO

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Project description:The health risk from spaceflight-induced neuronal damage and potential adverse neurovascular effects is a chief concern. More recently, 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 of neuroinflammation panel for inflammation, 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 Space-X 12 for a 35-day mission. Within 38+4 hours of splashdown, mice were returned to Earth alive. Brain tissues were collected for analysis. Habitat ground control (GC) mice were maintained on Earth in flight hardware cages. A novel digital color-coded barcode counting technology (NanoStringTM) was used to evaluate gene expression profiles in the spaceflight mouse brain. The Neuroinflammation panel includes 757 genes covering the core pathways and processes that define neuroimmune interactions. A set of 54 differently expressed genes (p<0.05) significantly segregates the GC group from flight (FLT) group. Many pathways associated with cellular stress, inflammation, apoptosis, and metabolism were significantly altered by flight conditions. Genes supporting neuronal synaptic signaling and migration were significantly downregulated in FLT compared to the GC mice. 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 antiviral signaling, reactive oxygen species (ROS) generation, and bacterial immune response were significantly downregulated. These data indicate that neuroinflammation and altered immune reactions may be closely associate with spaceflight-induced stress response and have an impact on the neuronal function that may result in chronic neuroinflammation and late neurodegeneration.

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Gene responses in mouse brain to long-term exposure to microgravity

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