Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Chronic Intermittent Hypoxia Increases Alveolar Surface Area in Adult Mice

ABSTRACT: Obstructive sleep apnea (OSA) leads to increased cardiovascular morbidity and mortality, which have been attributed to intermittent hypoxia (IH). The effects of IH on lung structure and function are unknown. We used a mouse model of chronic IH, which mimics the O2 profile in patients with OSA. We exposed adult C57BL/6J mice to 3 months of IH with an FIO2 nadir of 5%, 60 times/hr during the 12hr light phase. Control mice were exposed to room air. Gene microarrays were performed in a separate subset of animals (IH, n = 5; control, n = 5). Total RNA was isolated from lung tissue using the Trizol Reagent method, gene microarrays were performed with the Affymetrix GeneChipÂ® Mouse Genome 430A 2.0 Array (MG 430A 2.0; Affymetrix, Inc., Santa Clara, CA) and analyzed using Significance Analysis of Microarray (SAM) software.

ORGANISM(S): Mus musculus

SUBMITTER: Dmitry Grigoryev

PROVIDER: E-GEOD-21409 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Chronic intermittent hypoxia induces lung growth in adult mice.

Reinke Christian C Bevans-Fonti Shannon S Grigoryev Dmitry N DN Drager Luciano F LF Myers Allen C AC Wise Robert A RA Schwartz Alan R AR Mitzner Wayne W Polotsky Vsevolod Y VY

American journal of physiology. Lung cellular and molecular physiology 20101203 2

Obstructive sleep apnea (OSA) increases cardiovascular morbidity and mortality, which have been attributed to intermittent hypoxia (IH). The effects of IH on lung structure and function are unknown. We used a mouse model of chronic IH, which mimics the O(2) profile in patients with OSA. We exposed adult C57BL/6J mice to 3 mo of IH with a fraction of inspired oxygen (F(I)(O(2))) nadir of 5% 60 times/h during the 12-h light phase. Control mice were exposed to room air. Lung volumes were measured b ...[more]

PMID: 21131398

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Project description:The long-term effects of neonatal intermittent hypoxia (IH), an accepted model of apnea-induced hypoxia, are unclear. We have previously shown lasting âprogrammingâ effects on the HPA axis in adult rats exposed to neonatal IH. We hypothesized that neonatal rat exposure to IH will subsequently result in a heightened inflammatory state in the adult. Rat pups were exposed to normoxia (control) or six cycles of 5% IH or 10% IH over one hour daily from postnatal day 2 â 6. Plasma samples from blood obtained at 114 days of age were analyzed by assessing the capacity to induce transcription in a healthy peripheral blood mononuclear cell (PBMC) population and read using a high-density microarray. The analysis of plasma from adult rats previously exposed to neonatal 5% IH vs. 10% IH resulted in 2,579 significantly regulated genes including increased expression of Cxcl1, Cxcl2, Ccl3, Il1a, and Il1b. We conclude that neonatal exposure to intermittent hypoxia elicits a long-lasting programming effect in the adult resulting in an upregulation of inflammatory-related genes. Apnea is the most common cause of neonatal hypoxia affecting about 50% of preterm births (30 Ã¢ÂÂ 31 weeks), usually due to immature respiratory development. Upregulation of inflammatory genes and pathways in children 7 Ã¢ÂÂ 10 years of age has been shown, and there is a known increased risk of insulin resistance in adulthood when the fetus is exposed to maternal hypoxia, but the mechanism is unclear. The long-term metabolic, endocrine, and immunological effects of neonatal intermittent hypoxia (IH) exposure, an accepted model of apnea-induced hypoxia, have not been thoroughly evaluated. Recent studies in rats have shown that perinatal IH exposure can result in oxidative stress, causing a permanent immune response subsequently resulting in features of diabetes mellitus. We have previously examined adult rats exposed to neonatal intermittent hypoxia and perinatal continuous hypoxia, and have found lasting Ã¢ÂÂprogrammingÃ¢ÂÂ effects on the HPA axis. We now assess the long term effects of an accepted model of apnea-induced hypoxia using a validated transcriptional bioassay to study the extracellular milieu of adult rats exposed to neonatal intermittent hypoxia. We hypothesize that exposure to neonatal intermittent hypoxia will result in an increased inflammatory state in the adult as a result of long-lasting programming. Sprague-Dawley (SD) rat pups were treated with neonatal normoxia (21% O2, control), 5% intermittent hypoxia (IH), or 10% IH on postnatal days (PD) 2-6, daily over 1 hr. They were reared normally by birth dams and weaned at PD22. Males were allowed to mature and sacrificed at age PD114 after an overnight fast. Whole blood collected by decapitation into tubes with EDTA, and plasma saved for further analysis. Two adult (~180 day) male Brown Norway (BN) rats served as PBMC donors. Cells were incubated with 20% plasma that was either autologous BN (self-control), or one of 3 pools: a) SD normoxic N=8, b) SD 5% IH treated N=5, and c) SD 10% IH N=3.

Project description:The long-term effects of neonatal intermittent hypoxia (IH), an accepted model of apnea-induced hypoxia, are unclear. We have previously shown lasting “programming” effects on the HPA axis in adult rats exposed to neonatal IH. We hypothesized that neonatal rat exposure to IH will subsequently result in a heightened inflammatory state in the adult. Rat pups were exposed to normoxia (control) or six cycles of 5% IH or 10% IH over one hour daily from postnatal day 2 – 6. Plasma samples from blood obtained at 114 days of age were analyzed by assessing the capacity to induce transcription in a healthy peripheral blood mononuclear cell (PBMC) population and read using a high-density microarray. The analysis of plasma from adult rats previously exposed to neonatal 5% IH vs. 10% IH resulted in 2,579 significantly regulated genes including increased expression of Cxcl1, Cxcl2, Ccl3, Il1a, and Il1b. We conclude that neonatal exposure to intermittent hypoxia elicits a long-lasting programming effect in the adult resulting in an upregulation of inflammatory-related genes. Apnea is the most common cause of neonatal hypoxia affecting about 50% of preterm births (30 – 31 weeks), usually due to immature respiratory development. Upregulation of inflammatory genes and pathways in children 7 – 10 years of age has been shown, and there is a known increased risk of insulin resistance in adulthood when the fetus is exposed to maternal hypoxia, but the mechanism is unclear. The long-term metabolic, endocrine, and immunological effects of neonatal intermittent hypoxia (IH) exposure, an accepted model of apnea-induced hypoxia, have not been thoroughly evaluated. Recent studies in rats have shown that perinatal IH exposure can result in oxidative stress, causing a permanent immune response subsequently resulting in features of diabetes mellitus. We have previously examined adult rats exposed to neonatal intermittent hypoxia and perinatal continuous hypoxia, and have found lasting “programming” effects on the HPA axis. We now assess the long term effects of an accepted model of apnea-induced hypoxia using a validated transcriptional bioassay to study the extracellular milieu of adult rats exposed to neonatal intermittent hypoxia. We hypothesize that exposure to neonatal intermittent hypoxia will result in an increased inflammatory state in the adult as a result of long-lasting programming.

Dataset Information

Chronic Intermittent Hypoxia Increases Alveolar Surface Area in Adult Mice

Publications

Chronic intermittent hypoxia induces lung growth in adult mice.

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