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Regional genome 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 the brain against subsequent ischemia, this study examined the effects of brief hypoxia on the whole genome transcriptional response in adult mouse brain.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-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.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.

SUBMITTER: Xu H

PROVIDER: S-EPMC3218040 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature

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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:In the avian brain, adult neurogenesis has been reported in the telencephalon of several species, but the functional significance of this trait is still ambiguous. Homing pigeons (Columba livia f.d.) are well-known for their navigational skills. Their brains are functionally adapted to homing with, e.g., larger hippocampi. So far, no comprehensive mapping of adult neuro- and gliogenesis or studies of different developmental neuronal stages in the telencephalon of homing pigeons exists, although comprehensive analyses in various species surely will result in a higher understanding of the functional significance of adult neurogenesis. Here, adult, free flying homing pigeons were treated with 5-bromo-deoxyuridine (BrdU) to label adult newborn cells. Brains were dissected and immunohistochemically processed with several markers (GFAP, Sox2, S100ß, Tbr2, DCX, Prox1, Ki67, NeuN, Calbindin, Calretinin) to study different stages of adult neurogenesis in a quantitative and qualitative way. Therefore, immature and adult newborn neurons and glial cells were analyzed along the anterior-posterior axis. The analysis proved the existence of different neuronal maturation stages and showed that immature cells, migrating neurons and adult newborn neurons and glia were widely and regionally unequally distributed. Double- and triple-labelling with developmental markers allowed a stage classification of adult neurogenesis in the pigeon brain (1: continuity of stem cells/proliferation, 2: fate specification, 3: differentiation/maturation, 4: integration). The most adult newborn neurons and glia were found in the intercalated hyperpallium (HI) and the hippocampal formation (HF). The highest numbers of immature (DCX+) cells were detected in the nidopallium (N). Generally, the number of newborn glial cells exceeded the number of newborn neurons. Individual structures (e.g., HI, N, and HF) showed further variations along the anterior-posterior axis. Our qualitative classification and the distribution of maturing cells in the forebrain support the idea that there is a functional specialization, respectively, that there is a link between brain-structure and function, species-specific requirements and adult neurogenesis. The high number of immature neurons also suggests a high level of plasticity, which points to the ability for rapid adaption to environmental changes through additive mechanisms. Furthermore, we discuss a possible influence of adult neurogenesis on spatial cognition.

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Regional genome transcriptional response of adult mouse brain to hypoxia.

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Regional genome transcriptional response of adult mouse brain to hypoxia.

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