title: Gene expression profile of the hippocampus of rats subjected to chronic immobilization stress.
abstract: OBJECTIVE
  This study systematically investigated the effect of chronic stress on the hippocampus and its damage mechanism at the whole genome level.
  
  
  METHODS
  The rat whole genome expression chips (Illumina) were used to detect gene expression differences in the hippocampus of rats subjected to chronic immobilization stress (daily immobilization stress for 3 h, for 7 or 21 days). The hippocampus gene expression profile was studied through gene ontology and signal pathway analyses using bioinformatics. A differentially expressed transcription regulation network was also established. Real-time quantitative polymerase chain reaction (RT-PCR) was used to verify the microarray results and determine expression of the Gabra1, Fadd, Crhr2, and Cdk6 genes in the hippocampal tissues.
  
  
  RESULTS
  Compared to the control group, 602 differentially expressed genes were detected in the hippocampus of rats subjected to stress for 7 days, while 566 differentially expressed genes were expressed in the animals experiencing stress for 21 days. The stress significantly inhibited the primary immune system functions of the hippocampus in animals subjected to stress for both 7 and 21 days. Immobilization activated the extracellular matrix receptor interaction pathway after 7 day exposure to stress and the cytokine-cytokine receptor interaction pathway. The enhanced collagen synthesis capacity of the hippocampal tissue was the core molecular event of the stress regulation network in the 7-day group, while the inhibition of hippocampal cell growth was the core molecular event in the 21-day group. For the Gabra1, Fadd, Crhr2, and Cdk6 genes, RT-PCR results were nearly in line with gene chip assay results.
  
  
  CONCLUSIONS
  During the 7-day and 21-day stress processes, the combined action of polygenic, multilevel, and multi-signal pathways leads to the disorder of the immunologic functions of the hippocampus, hippocampal apoptosis, and proliferation disequilibrium.
authors.affiliation: School of Pre-clinical Medicine, Beijing University of Chinese Medicine, Beijing, China.
authors.forename: Xiao-Hong
authors.initials: XH
authors.lastname: Li
authors.forename: Jia-Xu
authors.initials: JX
authors.lastname: Chen
authors.forename: Guang-Xin
authors.initials: GX
authors.lastname: Yue
authors.forename: Yue-Yun
authors.initials: YY
authors.lastname: Liu
authors.forename: Xin
authors.initials: X
authors.lastname: Zhao
authors.forename: Xiao-Ling
authors.initials: XL
authors.lastname: Guo
authors.forename: Qun
authors.initials: Q
authors.lastname: Liu
authors.forename: You-Ming
authors.initials: YM
authors.lastname: Jiang
authors.forename: Ming-Hua
authors.initials: MH
authors.lastname: Bai
mesh_terms: D000818:Animals; D015536:Down-Regulation / Q000235:genetics; D005109:Extracellular Matrix / Q000235:genetics; D053263:Gene Regulatory Networks / Q000235:genetics; D006624:Hippocampus / Q000378:metabolism*; D007103:Immobilization; D008297:Male; D058977:Molecular Sequence Annotation; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics; D013312:Stress, Physiological / Q000235:genetics*; D014158:Transcription, Genetic; D059467:Transcriptome; D015854:Up-Regulation / Q000235:genetics
references.citation: Arthritis Res Ther. 2005;7(1):29-37
references.pmid: 15642151
references.citation: Cell. 1994 Jan 28;76(2):287-99
references.pmid: 8293464
references.citation: Nat Immunol. 2007 Sep;8(9):950-7
references.pmid: 17676044
references.citation: J Neurosci. 2005 Jul 6;25(27):6401-8
references.pmid: 16000631
references.citation: Cell Mol Neurobiol. 2008 Feb;28(2):237-44
references.pmid: 17636405
references.citation: Am J Physiol Gastrointest Liver Physiol. 2006 Apr;290(4):G827-38
references.pmid: 16537974
references.citation: PLoS Comput Biol. 2007 Mar 30;3(3):e61
references.pmid: 17397256
references.citation: Exp Neurol. 2006 Dec;202(2):324-35
references.pmid: 16899244
references.citation: J Neuroimmunol. 2002 Apr;125(1-2):5-14
references.pmid: 11960635
references.citation: Immunology. 2002 Aug;106(4):517-25
references.pmid: 12153515
references.citation: Biol Psychiatry. 1999 Apr 1;45(7):797-805
references.pmid: 10202566
references.citation: J Allergy Clin Immunol. 2009 Jun;123(6):1244-52.e2
references.pmid: 19439349
references.citation: Biol Psychiatry. 2003 Sep 1;54(5):499-503
references.pmid: 12946878
references.citation: Mech Ageing Dev. 2002 Feb;123(4):313-26
references.pmid: 11744043
references.citation: Immunol Today. 1994 Nov;15(11):504-11
references.pmid: 7802919
references.citation: Nature. 2004 Aug 26;430(7003):1034-9
references.pmid: 15329723
references.citation: Curr Opin Immunol. 2006 Jun;18(3):349-56
references.pmid: 16616472
references.citation: Biochem Biophys Res Commun. 2001 Mar;281(5):1220-5
references.pmid: 11243865
references.citation: J Immunol. 2009 Dec 1;183(11):7006-13
references.pmid: 19915054
references.citation: Genome Res. 2005 Aug;15(8):1034-50
references.pmid: 16024819
references.citation: J Immunol. 1998 Mar 15;160(6):2700-5
references.pmid: 9510169
references.citation: Nature. 2008 Dec 18;456(7224):989-92
references.pmid: 19011614
references.citation: J Clin Invest. 1974 Dec;54(6):1337-43
references.pmid: 4612058
references.citation: Oncogene. 1999 Feb 11;18(6):1297-302
references.pmid: 10022811
references.citation: J Am Geriatr Soc. 2002 Dec;50(12):2041-56
references.pmid: 12473019
references.citation: Clin Immunol. 2005 Nov;117(2):104-11
references.pmid: 16214080
references.citation: Adv Immunol. 2005;87:1-25
references.pmid: 16102570
references.citation: J Immunol. 1986 Apr 1;136(7):2348-57
references.pmid: 2419430
references.citation: Nat Genet. 2000 Apr;24(4):410-4
references.pmid: 10742108
references.citation: Proc Natl Acad Sci U S A. 2000 Aug 29;97(18):10026-31
references.pmid: 10944199
references.citation: Trends Endocrinol Metab. 2002 Dec;13(10):436-44
references.pmid: 12431840
references.citation: Nat Immunol. 2008 Dec;9(12):1347-55
references.pmid: 18997793
references.citation: J Med Invest. 2004 Aug;51(3-4):146-53
references.pmid: 15460900
references.citation: Brain Behav Immun. 2005 Sep;19(5):404-12
references.pmid: 16061150
references.citation: Blood. 2000 Sep 15;96(6):2277-83
references.pmid: 10979977
references.citation: Cell Mol Neurobiol. 2008 Aug;28(5):745-55
references.pmid: 17647101
references.citation: Vet Immunol Immunopathol. 2002 Aug;87(1-2):79-87
references.pmid: 12052345
references.citation: Curr Opin Immunol. 2005 Feb;17(1):65-70
references.pmid: 15653313
references.citation: FASEB J. 1998 Jul;12(10):801-11
references.pmid: 9657520
references.citation: Genome Res. 2003 Nov;13(11):2498-504
references.pmid: 14597658
references.citation: Blood. 2006 Jan 1;107(1):197-204
references.pmid: 16160012
references.citation: Oncogene. 2004 Oct 18;23(48):7990-8000
references.pmid: 15489916
references.citation: Mol Cell Endocrinol. 1997 Aug 8;131(2):233-40
references.pmid: 9296382
references.citation: J Immunotoxicol. 2008 Jan;5(1):43-6
references.pmid: 18382857
references.citation: Sheng Li Xue Bao. 1996 Aug;48(4):348-54
references.pmid: 9389197
references.citation: J Mol Endocrinol. 2005 Jun;34(3):597-601
references.pmid: 15956331
references.citation: Endocrinology. 1999 Sep;140(9):3981-91
references.pmid: 10465267
references.citation: J Mol Med (Berl). 1999 Nov;77(11):769-80
references.pmid: 10619437
references.citation: Curr Opin Immunol. 2007 Dec;19(6):652-7
references.pmid: 17766098
references.citation: Immunol Lett. 2001 Apr 2;76(3):153-61
references.pmid: 11306142
references.citation: J Neurotrauma. 1992 Mar;9 Suppl 1:S9-25
references.pmid: 1588635
references.citation: Endocrinology. 1998 Apr;139(4):1810-4
references.pmid: 9528966
references.citation: Nat Genet. 2000 Apr;24(4):403-9
references.pmid: 10742107
references.citation: J Neuroimmunol. 2003 Aug;141(1-2):58-64
references.pmid: 12965254
references.citation: Clin Immunol. 2006 Sep;120(3):260-71
references.pmid: 16765091
references.citation: Exp Neurol. 2008 Feb;209(2):343-52
references.pmid: 17727844
references.citation: J Neurosci. 1998 Sep 15;18(18):7462-73
references.pmid: 9736665
references.citation: Nucleic Acids Res. 2007 Jul;35(Web Server issue):W253-8
references.pmid: 17478497
references.citation: Toxicology. 2000 Jan 17;142(3):189-201
references.pmid: 10667890
references.citation: J Mol Med (Berl). 2005 Aug;83(8):587-95
references.pmid: 15821901
references.citation: Arch Neurol. 1964 Mar;10:233-48
references.pmid: 14106980
references.citation: Annu Rev Immunol. 2000;18:309-45
references.pmid: 10837061
references.citation: Arch Gen Psychiatry. 2000 Oct;57(10):925-35
references.pmid: 11015810
references.citation: Biochem Biophys Res Commun. 1996 Sep 13;226(2):329-34
references.pmid: 8806635
references.citation: Neuroimage. 2007 Apr 1;35(2):795-803
references.pmid: 17275340
references.citation: Blood. 2000 Feb 15;95(4):1370-7
references.pmid: 10666213
references.citation: Immunol Res. 2004;30(3):261-77
references.pmid: 15531769
references.citation: Science. 1995 Sep 1;269(5228):1236-41
references.pmid: 7544491
references.citation: J Immunol. 2003 Nov 15;171(10):5470-81
references.pmid: 14607953
references.citation: Immunol Rev. 2004 Dec;202:33-48
references.pmid: 15546384
references.citation: Crit Care Med. 2002 Jan;30(1 Supp):S64-S73
references.pmid: 11891406
references.citation: EMBO J. 2004 Jul 7;23(13):2577-85
references.pmid: 15192708
references.citation: Arterioscler Thromb Vasc Biol. 2005 Jun;25(6):1135-41
references.pmid: 15817882
references.citation: Cardiovasc Res. 2007 Aug 1;75(3):555-65
references.pmid: 17531211
references.citation: J Immunol. 1997 Jun 15;158(12):5589-95
references.pmid: 9190905
references.citation: Circ Res. 2000 Sep 15;87(6):508-15
references.pmid: 10988244
references.citation: Immunol Rev. 2005 Oct;207:242-60
references.pmid: 16181341
references.citation: J Immunol. 2000 Feb 15;164(4):1768-74
references.pmid: 10657623
references.citation: J Neuroimmunol. 1993 Feb;42(2):193-7
references.pmid: 8429104
references.citation: Zhongguo Ying Yong Sheng Li Xue Za Zhi. 2004 Feb;20(1):71-4
references.pmid: 21162314
references.citation: J Clin Invest. 2009 Dec;119(12):3573-85
references.pmid: 19920355
references.citation: Methods Mol Biol. 2007;377:223-42
references.pmid: 17634620
references.citation: J Exp Med. 2009 Aug 3;206(8):1653-60
references.pmid: 19596803
references.citation: J Biochem. 1997 Feb;121(2):197-205
references.pmid: 9089390
references.citation: Neuropsychobiology. 1993;28(1-2):87-90
references.pmid: 8255416