Journal of Molecular Neuroscience

, Volume 42, Issue 2, pp 154–161

Gene Network Analysis to Determine the Effects of Antioxidant Treatment in a Rat Model of Neonatal Hypoxic-Ischemic Encephalopathy

  • Toshio Kojima
  • Yuto Ueda
  • Naoki Adati
  • Aya Kitamoto
  • Akira Sato
  • Ming-Chih Huang
  • Jesmine Noor
  • Hiroshi Sameshima
  • Tsuyomu Ikenoue
Article

Abstract

Neonatal hypoxic-ischemic (HI) encephalopathy can lead to severe brain damage, and is a common cause of neurological handicaps in adulthood. HI can be resolved by the administration of an antioxidant such as 3-methyl-1-phenyl-2-pyrazolin-5-one (MCI-186). In the present study, we performed comprehensive gene expression and gene network analyses using a DNA microarray to elucidate the molecular events responsible for the selective vulnerability of neurons in neonatal HI brain insult and to examine the underlying mechanisms of the effect of MCI-186 on the pathophysiological events in this condition. We used the modified Levine method (Rice model), which has been widely used as an animal model of this condition. A large difference in gene expression was observed between the Rice model and the control group. Up- and downregulated genes after the HI brain insult were mainly related to immune responses and cell death, and neuronal activity, respectively. The effect of MCI-186 administration on gene expression was much less than and contrary to that of the HI brain insult, reflecting the protective effect of MCI-186 in HI brain insult.

Keywords

Hypoxic-ischemic encephalopathy Antioxidant Gene expression DNA microarray Gene network 

Supplementary material

12031_2010_9337_MOESM1_ESM.xls (64 kb)
Supplementary Table S1RICE cluster0 genes (XLS 64 kb)
12031_2010_9337_MOESM2_ESM.xls (146 kb)
Supplementary Table S2RICE cluster1 genes (XLS 146 kb)
12031_2010_9337_MOESM3_ESM.xls (62 kb)
Supplementary Table S3RICE cluster2 genes (XLS 62 kb)
12031_2010_9337_MOESM4_ESM.xls (21 kb)
Supplementary Table S4MCI-186 upregulated genes (XLS 21 kb)
12031_2010_9337_MOESM5_ESM.xls (16 kb)
Supplementary Table S5MCI-186 downregulated genes (XLS 16 kb)

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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Toshio Kojima
    • 1
    • 2
  • Yuto Ueda
    • 3
  • Naoki Adati
    • 1
  • Aya Kitamoto
    • 1
  • Akira Sato
    • 1
    • 2
  • Ming-Chih Huang
    • 1
    • 5
  • Jesmine Noor
    • 4
  • Hiroshi Sameshima
    • 4
  • Tsuyomu Ikenoue
    • 4
  1. 1.Computational Systems Biology Research GroupAdvanced Science InstituteKanagawaJapan
  2. 2.CREST, Japan Science and Technology Agency (JST)SaitamaJapan
  3. 3.Section of Psychiatry, Department of Clinical Neuroscience, Faculty of MedicineUniversity of MiyazakiMiyazakiJapan
  4. 4.Section of Obstetrics and Gynecology, Department of Reproductive and Developmental Medicine, Faculty of MedicineUniversity of MiyazakiMiyazakiJapan
  5. 5.Department of Biological Sciences and TechnologyNational University of TainanTainanRepublic of China

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