Experimental Brain Research

, Volume 191, Issue 3, pp 289–300

Effect of microgravity on gene expression in mouse brain

  • Antonio Frigeri
  • Dumitru A. Iacobas
  • Sanda Iacobas
  • Grazia Paola Nicchia
  • Jean Francois Desaphy
  • Diana Conte Camerino
  • Maria Svelto
  • David C. Spray
Research Article

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.

Keywords

Microgravity Hindlimb-unloaded cDNA microarray Brain Space flight Gravitational force Microgravitational adaptations 

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

Supplementary material

221_2008_1523_MOESM1_ESM.doc (436 kb)
All regulated genes in HU versus control brain (DOC 436 kb)

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Antonio Frigeri
    • 1
  • Dumitru A. Iacobas
    • 2
  • Sanda Iacobas
    • 2
  • Grazia Paola Nicchia
    • 1
  • Jean Francois Desaphy
    • 3
  • Diana Conte Camerino
    • 3
  • Maria Svelto
    • 1
  • David C. Spray
    • 2
  1. 1.Department of General and Environmental Physiology, Centre of Excellence in Comparative Genomics (CEGBA)University of BariBariItaly
  2. 2.Department of NeuroscienceAlbert Einstein College of MedicineBronxUSA
  3. 3.Department of PharmacobiologyUniversity of BariBariItaly

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