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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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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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