Unknown,Transcriptomics,Genomics,Proteomics

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Transcriptional Response of Adult Mouse Brain to Hypoxia

ABSTRACT: Since normal brain function depends upon continuous oxygen delivery and short periods of hypoxia can precondition against subsequent ischemia, this study examined the effects of brief hypoxia on the whole genome transcriptional response in adult mouse brain. Genomic expression profiling was perfromed for individual brain regions of the adult mice following the entire time course of hypoxia preconditioning. Adult C57BL/6 male mice were exposed to systemic preconditioning hypoxia (8% O2 ) for 3 hr and allowed to recover in normoxia for 24 hr. The mouse brains were removed and dissected into individual brain regions at multiple time points during the 3hr hypoxia and subsequent 24hr reoxygenation periods. Total RNA was purified from the human whole blood or individual mouse brain regions. Genomic scale gene expression was then measured with Affymetrix Mouse Expression 430 2.0 arrays.

ORGANISM(S): Mus musculus

SUBMITTER: Huichun Xu

PROVIDER: E-GEOD-19709 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Regional genome transcriptional response of adult mouse brain to hypoxia.

Xu Huichun H Lu Aigang A Sharp Frank R FR

BMC genomics 20111011

<h4>Background</h4>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.<h4>Result</h4>Pronounced changes of gene expression occurred after 3 hours of hypoxia (8% O(2)) and after 1 hour of re-oxygenation in all brain regions. The hypoxia-responsive genes were predominantly up-regulate ...[more]

PMID: 21988864

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Project description:Background: Constant hypoxia (CH) and intermittent hypoxia (IH) occur during several pathological conditions such as asthma and obstructive sleep apnea. Our research is focused on understanding the molecular mechanisms that lead to injury or adaptation to hypoxic stress using Drosophila as a model system. Our current genome-wide study is designed to investigate gene expression changes and identify protective mechanism(s) in D. melanogaster after exposure to severe (1% O2) intermittent or constant hypoxia. Methodology/Principal Findings: Our microarray analysis has identified multiple gene families that are up- or down-regulated in response to acute CH or IH. We observed distinct responses to IH and CH in gene expression that varied in the number of genes and type of gene families. We then studied the role of candidate genes (up-or down-regulated) in hypoxia tolerance (adult survival) for longer periods (CH-7 days, IH-10 days) under severe CH or IH. Heat shock proteins up-regulation (specifically Hsp23 and Hsp70) led to a significant increase in adult survival (as compared to controls) of P-element lines during CH. In contrast, during IH treatment the up-regulation of Mdr49 and l(2)08717 genes (P-element lines) provided survival advantage over controls. This suggests that the increased transcript levels following treatment with either paradigm play an important role in tolerance to severe hypoxia. Furthermore, by over-expressing Hsp70 in specific tissues, we found that up-regulation of Hsp70 in heart and brain play critical role in tolerance to CH in flies. Conclusions/Significance: We observed that the gene expression response to IH or CH is specific and paradigm-dependent. We have identified several genes Hsp23, Hsp70, CG1600, l(2)08717 and Mdr49 that play an important role in hypoxia tolerance whether it is in CH or IH. These data provide further clues about the mechanisms by which IH or CH lead to cell injury and morbidity or adaptation and survival. Expression profiles were determined by expression arrays in Drosophila melanogaster following acute constant or intermittent hypoxia. Three groups of samples were included in this analysis (3 x control, 3x CH treated and 3 x IH treated samples).

Dataset Information

Transcriptional Response of Adult Mouse Brain to Hypoxia

Publications

Regional genome transcriptional response of adult mouse brain to hypoxia.

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