Effect of microgravity on gene expression in mouse brain

Abstract

Changes in gravitational force such as that experienced by astronauts during space flight induce a redistribution of fluids from the caudad to the cephalad portion of the body together with an elimination of normal head-to-foot hydrostatic pressure gradients. To assess brain gene profile changes associated with microgravity and fluid shift, a large-scale analysis of mRNA expression levels was performed in the brains of 2-week control and hindlimb-unloaded (HU) mice using cDNA microarrays. Although to different extents, all functional categories displayed significantly regulated genes indicating that considerable transcriptomic alterations are induced by HU. Interestingly, the TIC class (transport of small molecules and ions into the cells) had the highest percentage of up-regulated genes, while the most down-regulated genes were those of the JAE class (cell junction, adhesion, extracellular matrix). TIC genes comprised 16% of those whose expression was altered, including sodium channel, nonvoltage-gated 1 beta (Scnn1b), glutamate receptor (Grin1), voltage-dependent anion channel 1 (Vdac1), calcium channel beta 3 subunit (Cacnb3) and others. The analysis performed by GeneMAPP revealed several altered protein classes and functional pathways such as blood coagulation and immune response, learning and memory, ion channels and cell junction. In particular, data indicate that HU causes an alteration in hemostasis which resolves in a shift toward a more hyper-coagulative state with an increased risk of venous thrombosis. Furthermore, HU treatment seems to impact on key steps of synaptic plasticity and learning processes.

Fig. 1

Percent of regulated (a, c) out of quantified (b, d) genes in the brain of HU mice. Note that all functional categories and all chromosomes were affected as a result of the hindlimb suspension, with TIC genes showing highest percentage of up-regulated genes and JAE the lowest

Fig. 2

Histograms of the relative expression variability in brain of control (CT) and tail- suspended (HU) mice. Note the substantial reduction of the median relative expression variability in HU mice compared to that of CT mice indicating a significant increase of the overall control of transcripts’ abundance