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REVIEW ARTICLE
Year : 2017  |  Volume : 2  |  Issue : 1  |  Page : 14-17

Epigenetic programming of autonomic functions in an experimental model of apnea of prematurity


Institute for Integrative Physiology and Center for Systems Biology of O2Sensing, Biological Science Division, University of Chicago, Chicago, USA

Correspondence Address:
Nanduri R Prabhakar
Institute for Integrative Physiology, Biological Science Division, 5841 S. Maryland Avenue, MC 5068, Room No. 711, Chicago, IL 60637
USA
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/bjhs.bjhs_8_17

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Intermittent hypoxia (IH) is a hallmark manifestation of recurrent apneas, which is a major clinical problem in infants born preterm. Carotid body (CB) chemoreflex and catecholamine (CA) secretion from adrenal medullary chromaffin cells (AMCs) are two major mechanisms contributing to the maintenance of cardiorespiratory homeostasis during hypoxia. The purpose of this article is to highlight recent studies showing how neonates experiencing IH affect the CB and AMC function and their consequences in adult life. To simulate apneas, rat pups were treated with IH consisting of alternating cycles of hypoxia (1.5% O2) for 15 s and room air for 5 min, 8 h/day from ages P0–P10. Rats treated neonatal IH displayed augmented CB response to hypoxia and augmented CA secretion from AMC. Rats treated for 10 days of IH in the neonatal period were allowed to grow into adulthood. Remarkably, the effects of neonatal IH on CB and AMC persisted in the adulthood. Moreover, adult rats that were exposed to IH in neonatal period exhibited hypertension, increased incidence apnea. Analysis of the underlying molecular mechanisms revealed re-programming of the redox state by epigenetic mechanisms involving suppression of transcription of antioxidant enzyme genes by DNA hypermethylation. DNA hypomethylating agents might offer a novel therapeutic intervention to prevent early onset of cardiorespiratory morbidities caused by neonatal IH.


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