Intermittent neonatal hypoxia elicits the upregulation of inflammatory-related genes in the adult rat through long-lasting programming effects
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ABSTRACT: 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.
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE74145 | GEO | 2016/01/07
SECONDARY ACCESSION(S): PRJNA299161
REPOSITORIES: GEO
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