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Effect of microgravity on gene expression in mouse brain

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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.

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Abbreviations

CT:

Control

GES:

Gene expression stability

HU:

Hindlimb-unloaded

REV:

Relative estimated variability

CSD:

Cell cycle, shape, differentiation, death

[A apoptosis, C cell cycle (cyclin), D development, differentiation, organogenesis, G growth factors, hormones, cytokines, S shape, N oNcogenes, O others]

CYT:

Cytoskeleton

ENE:

Energy metabolism

MIT:

Mitochondrial proteins involved in cyclic acid cycle, respiratory chain

(L lipid metabolism, D degradation such as in peroxisomes, proteasome ubiquitination, G glycolysis, glycogenesis, O others)

JAE:

Cell junction, adhesion, extracellular matrix

[A antigens, integrins, G globulins and blood, M extracellular matrix, laminin, J junction and associated proteins, P proteases (such as metalloproteinases), O others]

RNA:

RNA processing

(M mRNA, R rRNA, T tRNA, MIT mitochondrial RNA)

SIG:

Cell signaling (G-proteins coupled receptors PKA PKC cAMP calcium MAPK SH2 SH3 Ca-binding proteins)

TIC:

Transport of small molecules and ions into the cells (transporters ion channels ionotropic receptors)

TRA:

Transcription

[D DNA transcription factors, P DNA processing (such as polymerases), O others]

TWC:

Transport of ions/molecules within the cells (vesicles, kinesin, endosomes, proteosomes, protein folding, lysosomes, nuclear transport)

UNK:

Function not yet assigned

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Acknowledgments

The financial support from the Italian Space Agency (I/R/372/02, OSMA) is gratefully acknowledged.

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Authors and Affiliations

  1. Department of General and Environmental Physiology, Centre of Excellence in Comparative Genomics (CEGBA), University of Bari, via Amendola 165/A, 70126, Bari, Italy

    Antonio Frigeri, Grazia Paola Nicchia & Maria Svelto

  2. Department of Neuroscience, Albert Einstein College of Medicine, 1410 Pelham Pkwy S, Bronx, NY, 10464, USA

    Dumitru A. Iacobas, Sanda Iacobas & David C. Spray

  3. Department of Pharmacobiology, University of Bari, 70126, Bari, Italy

    Jean Francois Desaphy & Diana Conte Camerino

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  1. Antonio Frigeri
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  2. Dumitru A. Iacobas
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Correspondence to Antonio Frigeri.

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All regulated genes in HU versus control brain (DOC 436 kb)

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Frigeri, A., Iacobas, D.A., Iacobas, S. et al. Effect of microgravity on gene expression in mouse brain. Exp Brain Res 191, 289–300 (2008). https://doi.org/10.1007/s00221-008-1523-5

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