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The genomic profile of the cerebral cortex after closed head injury in mice: effects of minocycline

  • Basic Neurosciences, Genetics and Immunology - Original Article
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Abstract

Microarray analysis was used to delineate gene expression patterns and profile changes following traumatic brain injury (TBI) in mice. A parallel microarray analysis was carried out in mice with TBI that were subsequently treated with minocycline, a drug proposed as a neuroprotectant in other neurological disorders. The aim of this comparison was to identify pathways that may be involved in secondary injury processes following TBI and potential specific pathways that could be targeted with second generation therapeutics for the treatment of neurotrauma patients. Gene expression profiles were measured with the compugen long oligo chip and real-time PCR was used to validate microarray findings. A pilot study of effect of minocycline on gene expression following TBI was also carried out. Gene ontology comparison analysis of sham TBI and minocycline treated brains revealed biological pathways with more genes differentially expressed than predicted by chance. Among 495 gene ontology categories, the significantly different gene ontology groups included chemokines, genes involved in cell surface receptor-linked signal transduction and pro-inflammatory cytokines. Expression levels of some key genes were validated by real-time quantitative PCR. This study confirms that multiple regulatory pathways are affected following brain injury and demonstrates for the first time that specific genes and molecular networks are affected by minocycline following brain injury.

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Acknowledgments

This study was supported by grants from the Victorian Trauma Foundation, the Victorian Neurotrauma Initiative and National Health and Medical Research Council of Australia project grant 234568

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Correspondence to Peter J. Crack.

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Appendix 1: Gene array abbreviations

Appendix 1: Gene array abbreviations

Adm :

adrenomedullin

Alx4 :

aristaless 4

Arg1 :

arginase 1, liver

Atf3 :

activating transcription factor 3

Bcl2a1a :

B-cell leukemia/lymphoma 2 related protein A1a

Btg2 :

B-cell translocation gene 2, anti-proliferative

Casp3 :

caspase 3

Casp8 :

caspase 8

Ccl12 :

chemokine (C–C motif) ligand 12

Ccl2 :

chemokine (C–C motif) ligand 2

Ccl24 :

chemokine (C–C motif) ligand 24

Ccl3 :

chemokine (C–C motif) ligand 3

Ccl4 :

chemokine (C–C motif) ligand 4

Ccl5 :

chemokine (C–C motif) ligand 5

Ccl6 :

chemokine (C–C motif) ligand 6

Ccl7 :

chemokine (C–C motif) ligand 7

Ccl8 :

chemokine (C–C motif) ligand 8

Ccl9 :

chemokine (C–C motif) ligand 9

Cd14 :

CD14 antigen

Cd52 :

CD52 antigen

Cd68 :

CD68 antigen

Cd72 :

CD72 antigen

Cd83 :

CD83 antigen

Cd86 :

CD86 antigen

Cebpb :

CCAAT/enhancer binding protein (C/EBP), beta

Cebpb :

CCAAT/enhancer binding protein (C/EBP), beta

Cebpb :

CCAAT/enhancer binding protein (C/EBP), beta

Ch25 h :

cholesterol 25-hydroxylase

Chst10 :

carbohydrate sulfotransferase 10

Csf3 :

colony stimulating factor 3 (granulocyte)

Cst10 :

cystatin 10 (chondrocytes)

Cxcl1 :

chemokine (C–X–C motif) ligand 1

Cxcl2 :

chemokine (C–X–C motif) ligand 2

Cyp2g1 :

cytochrome P450, family 2, subfamily g, polypeptide 1

Dnajb4 :

(2010306G19Rik): DnaJ (Hsp40) homolog, subfamily B, member 4

Enpp2 :

ectonucleotide pyrophosphatase/phosphodiesterase 2

Eprs :

glutamyl-prolyl-tRNA synthetase

Fas (Tnfrsf6) :

Fas (TNF receptor superfamily member)

Fas :

Fas (TNF receptor superfamily member)

Fcer1g :

Fc receptor, IgE, high affinity I, gamma polypeptide

Fcgr3 :

Fc receptor, IgG, low affinity III

Fgfrl1 :

fibroblast growth factor receptor-like 1

Fos :

FBJ osteosarcoma oncogene

Fosl1 :

fos-like antigen 1

Fpgt :

fucose-1-phosphate guanylyltransferase

Gadd45b :

growth arrest and DNA-damage-inducible 45 beta

Gadd45g :

growth arrest and DNA-damage-inducible 45 gamma

Gbp2 :

guanylate nucleotide binding protein 2

Hmox1 :

heme oxygenase (decycling) 1

Hoxa5 :

homeo box A5

Hsp110 :

heat shock protein 110

Ifi30 :

interferon gamma inducible protein 30

Ifrd1 :

interferon-related developmental regulator 1

Igfbp7 :

insulin-like growth factor binding protein 7

Il1α :

interleukin 1 alpha

Il1β :

interleukin 1 beta

Il6 :

interleukin 6

Inpp4a :

inositol polyphosphate-4-phosphatase, type I

Irgm (Ifi1) :

immunity-related GTPase family, M

Isg15 (G1p2) :

ISG15 ubiquitin-like modifier

Kbtbd5 :

kelch repeat and BTB (POZ) domain containing 5

Lzp-s :

P lysozyme structural

Myc :

myelocytomatosis oncogene

Nek7 :

NIMA (never in mitosis gene a)-related expressed kinase 7

Ngfβ :

nerve growth factor, beta

Npepps :

aminopeptidase puromycin sensitive

Npl :

N-acetylneuraminate pyruvate lyase

Nppb :

natriuretic peptide precursor type B

Nr3c1 :

nuclear receptor subfamily 3, group C, member 1

Odc1 :

ornithine decarboxylase, structural 1

Osmr :

oncostatin M receptor

Polr2l :

polymerase (RNA) II (DNA directed) polypeptide L

Ppp2r2α :

protein phosphatase 2 (formerly 2A), regulatory subunit B (PR 52), alpha isoform

Ppp3cα :

protein phosphatase 3, catalytic subunit, alpha isoform

Pros1 :

protein S (alpha)

Rest :

RE1-silencing transcription factor

S100a6 :

S100 calcium binding protein A6 (calcyclin)

S100a8 :

S100 calcium binding protein A8 (calgranulin A)

Serpine1 :

serine (or cysteine) peptidase inhibitor, clade E, member 1

Serpini1 :

serine (or cysteine) peptidase inhibitor, clade I, member 1

Socs3 :

suppressor of cytokine signaling 3

Stat3 :

signal transducer and activator of transcription 3

Tgm1 :

transglutaminase 1, K polypeptide

Tnfrsf12a :

tumor necrosis factor receptor superfamily, member 12a

Tnfrsf1a :

tumor necrosis factor receptor superfamily, member 1a

Tsc22d3 (Dsip1) :

TSC22 domain family 3

Ube4b :

ubiquitination factor E4B, UFD2 homolog (S. cerevisiae)

Ywhaq :

tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, theta polypeptide

Zfp36 :

zinc finger protein 36

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Crack, P.J., Gould, J., Bye, N. et al. The genomic profile of the cerebral cortex after closed head injury in mice: effects of minocycline. J Neural Transm 116, 1–12 (2009). https://doi.org/10.1007/s00702-008-0145-1

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  • DOI: https://doi.org/10.1007/s00702-008-0145-1

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