Regional genome transcriptional response of adult mouse brain to hypoxia

Huichun Xu, Aigang Lu, Frank R Sharp

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Background: Since normal brain function depends upon continuous oxygen delivery and short periods of hypoxia can precondition the brain against subsequent ischemia, this study examined the effects of brief hypoxia on the whole genome transcriptional response in adult mouse brain.Result: Pronounced changes of gene expression occurred after 3 hours of hypoxia (8% O2) and after 1 hour of re-oxygenation in all brain regions. The hypoxia-responsive genes were predominantly up-regulated in hindbrain and predominantly down-regulated in forebrain - possibly to support hindbrain survival functions at the expense of forebrain cognitive functions. The up-regulated genes had a significant role in cell survival and involved both shared and unshared signaling pathways among different brain regions. Up-regulation of transcriptional signaling including hypoxia inducible factor, insulin growth factor (IGF), the vitamin D3 receptor/retinoid X nuclear receptor, and glucocorticoid signaling was common to many brain regions. However, many of the hypoxia-regulated target genes were specific for one or a few brain regions. Cerebellum, for example, had 1241 transcripts regulated by hypoxia only in cerebellum but not in hippocampus; and, 642 (54%) had at least one hepatic nuclear receptor 4A (HNF4A) binding site and 381 had at least two HNF4A binding sites in their promoters. The data point to HNF4A as a major hypoxia-responsive transcription factor in cerebellum in addition to its known role in regulating erythropoietin transcription. The genes unique to hindbrain may play critical roles in survival during hypoxia.Conclusion: Differences of forebrain and hindbrain hypoxia-responsive genes may relate to suppression of forebrain cognitive functions and activation of hindbrain survival functions, which may coordinately mediate the neuroprotection afforded by hypoxia preconditioning.

Original languageEnglish (US)
Article number499
JournalBMC Genomics
Volume12
DOIs
StatePublished - Oct 11 2011

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Brain Hypoxia
Genome
Rhombencephalon
Prosencephalon
Brain
Cerebellum
Genes
Cytoplasmic and Nuclear Receptors
Cognition
Hypoxia
Binding Sites
Retinoid X Receptors
Calcitriol Receptors
Erythropoietin
Glucocorticoids
Hippocampus
Cell Survival
Intercellular Signaling Peptides and Proteins
Transcription Factors
Up-Regulation

ASJC Scopus subject areas

  • Biotechnology
  • Genetics

Cite this

Regional genome transcriptional response of adult mouse brain to hypoxia. / Xu, Huichun; Lu, Aigang; Sharp, Frank R.

In: BMC Genomics, Vol. 12, 499, 11.10.2011.

Research output: Contribution to journalArticle

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