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Cited by 37Neurological Disease Mechanisms and TreatmentsNeuroinflammation and Neurodegeneration MechanismsAcute Ischemic Stroke Management

Profiling of genes associated with transcriptional responses in mouse hippocampus after transient forebrain ischemia using high-density oligonucleotide DNA array

Nagata, Toshihito, Takahashi, Yasuo, Sugahara, Megumi, Murata, Akiko, Nishida, Yayoi, Ishikawa, Koichi, Asai, Satoshi·2004·Molecular Brain Research
DOI 10.1016/j.molbrainres.2003.10.023
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Abstract

Several cascades of changes in gene expression have been shown to be involved in the neuronal injury after transient cerebral ischemia; however, little is known about the profile of genes showing alteration of expression in a mouse model of transient forebrain ischemia. We analyzed the gene expression profile in the mouse hippocampus during 24 h of reperfusion, after 20 min of transient forebrain ischemia, using a high-density oligonucleotide DNA array. Using statistical filtration (Welch's ANOVA and Welch's t-test), we identified 25 genes with a more than 3.0-fold higher or lower level of expression on average, with statistical significance set at p<0.05, in at least one ischemia-reperfusion group than in the sham group. Using unsupervised clustering methods (hierarchical clustering and k-means clustering algorithms), we identified four types of gene expression pattern that may be associated with the response of cell populations in the hippocampus to an ischemic insult in this mouse model. Functional classification of the 25 genes demonstrated alterations of expression of several kinds of biological pathways, regulating transcription (Bhlhb2, Jun, c-fos, Egr1, Egr2, Fosb, Junb, Ifrd1, Neurod6), the cell cycle (c-fos, Fosb, Jun, Junb, Dusp1), stress response (Dusp1, Dnajb1, Dnaja4), chaperone activity (Dnajb1, Dnaja4) and cell death (Ptgs2, Gadd45g, Tdag51), in the mouse hippocampus by 24 h of reperfusion. Using hierarchical clustering analysis, we also found that the same 25 genes clearly discriminated between the sham group and the ischemia-reperfusion groups. The alteration of expression of 25 genes identified in this study suggests the involvement of these genes in the transcriptional response of cell populations in the mouse hippocampus after transient forebrain ischemia.

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Authors
Nagata, T., Takahashi, Y., Sugahara, M., Murata, A., Nishida, Y., Ishikawa, K., & Asai, S.
Affiliations
Nihon University (JP)
Corresponding author
Nagata, Toshihito
ORCID
Venue
Molecular Brain Research
Publisher
Elsevier BV
Published
2004-02
Volume
121
Issue
1-2
Pages
1-11
ISSN
0169-328X (ISSN-L)
DOI
10.1016/j.molbrainres.2003.10.023
OpenAlex
W1996618266
Cited by
37
References
48
Citations by year
2026: 1 · 2025: 1 · 2022: 1 · 2021: 1 · 2020: 2 · 2019: 1 · 2017: 1 · 2015: 1 · 2014: 1 · 2012: 1
FWCI
3.17
Type
journal article
Language
en
Open access
closed
Licence
Locations
  • Molecular Brain Research (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • School of Medicine
  • Ministry of Education, Culture, Sports, Science and Technology
  • Nihon University (14570777)
Topics
  • Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Health Sciences › Medicine › Epidemiology › Acute Ischemic Stroke Management
Keywords
transient forebrain ischemia, hippocampus, ischemia-reperfusion, gene expression profiling, transcriptional response, neuronal injury, c-fos, c-Jun, EGR1, EGR2, FosB, JunB, MKP-1, DNAJB1, chaperone activity, stress response, cell death, cell cycle, mouse model
MeSH terms
Analysis of Variance, Animals, Cell Cycle, Ischemic Attack, Transient, Disease Models, Animal, Hippocampus, Male, Mice, Inbred C57BL, Stress, Physiological, Transcription, Genetic, Gene Expression, Cluster Analysis, Cell Death, Molecular Chaperones, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, Mice

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