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 upregulated 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), voltagedependent anion channel 1 (Vdac1), calcium channel beta 3 subunit (Cacnb3) and others. The analysis performed by Gene-MAPP 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.

Effects of simulated microgravity on the expression of presynaptic proteins distorting the GABA/glutamate equilibrium – A proteomics approach

“…Previous studies using traditional 2DE coupled with MALDI‐TOF have shown that 7 days SM induces the down‐regulation of structural and metabolic proteins . Other studies using microarray analysis reported that 14 days of SM induced changes in synaptic genes . Our previous study showed that SM decreases SNARE‐related proteins in the hippocampus, leading to impaired learning and memory function.…”

Activation of nervous system development genes in bone marrow derived mesenchymal stem cells following spaceflight exposure

“…It is possible that the observed impairment of neurogenesis in microgravity‐exposed embryos could be ascribed more to an impairment of the progenitor/neural cell migration than to the intrinsic cell neural differentiation. Interestingly, cDNA microarray showed that hindlimb‐unloading treatment up‐regulated key steps of synaptic plasticity and learning process in mouse brain [Frigeri et al, 2008].…”

Gene Expression Microarrays in Microgravity Research: Toward the Identification of Major Space Genes

“…Frigeri et al examined gene expression in mouse brain after 2 weeks hindlimb supesension (Frigeri et al 2008). Using 27K cDNA microarrays, they found 592 statistically significant genes with 1.5 fold or higher differential regulation.…”