Genome-wide transcriptome profiling of region-specific vulnerability to oxidative stress in the hippocampus

Xinkun Wang, Ranu Pal, Xue wen Chen, Keshava N. Kumar, Ok Jin Kim, Elias K. Michaelis*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

Abstract

Neurons in the hippocampal CA1 region are particularly sensitive to oxidative stress (OS), whereas those in CA3 are resistant. To uncover mechanisms for selective CA1 vulnerability to OS, we treated organotypic hippocampal slices with duroquinone and compared transcriptional profiles of CA1 vs CA3 cells at various intervals. Gene Ontology and Biological Pathway analyses of differentially expressed genes showed that at all time points, CA1 had higher transcriptional activity for stress/inflammatory response, transition metal transport, ferroxidase, and presynaptic signaling activity, while CA3 had higher GABA-signaling, postsynaptic, and calcium and potassium channel activity. Real-time PCR and immunoblots confirmed the transcriptome data and the induction of OS by duroquinone in both hippocampal regions. Our functional genomics approach has identified in CA1 cells molecular pathways as well as unique genes, such as guanosine deaminase, lipocalin 2, synaptotagmin 4, and latrophilin 2, whose time-dependent induction following the initiation of OS may represent attempts at neurite outgrowth, synaptic recovery, and resistance against OS.

Original languageEnglish (US)
Pages (from-to)201-212
Number of pages12
JournalGenomics
Volume90
Issue number2
DOIs
StatePublished - Aug 2007

Keywords

  • CA1
  • CA3
  • Gene expression profiling
  • Hippocampus
  • Inflammation
  • Neurite outgrowth
  • Oxidative stress

ASJC Scopus subject areas

  • Genetics

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