Developmental programming of O2 sensing by neonatal intermittent hypoxia via epigenetic mechanisms

Recurrent apnea with intermittent hypoxia (IH) is a major clinical problem in infants born preterm. Carotid body chemo-reflex and catecholamine secretion from adrenal medullary chromaffin cells (AMC) are important for maintenance of cardio-respiratory homeostasis during hypoxia. This article highlig...

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Bibliographic Details
Published inRespiratory physiology & neurobiology Vol. 185; no. 1; pp. 105 - 109
Main Authors Nanduri, Jayasri, Prabhakar, Nanduri R.
Format Journal Article
LanguageEnglish
Published Elsevier B.V 01.01.2013
Subjects
Apnea
Apnea of prematurity
Calcium signalling
Cardio-respiratory morbidities
Carotid body
Catecholamines
Chromaffin cells
DNA
DNA methylation
Endothelin 1
epigenetics
Exocytosis
Histone modifications
Hypertension
Hypoxia
Infants
Medical Education
Morbidity
Neonates
Nervous system
Neurotransmitters/modulators
Oxidative stress
Pulmonary/Respiratory
Reactive oxygen species
Respiration
Secretion
Sleep disorders
Therapeutic applications
Neurotransmitters/modulators
Oxidative stress
Apnea of prematurity
DNA methylation
Cardio-respiratory morbidities
Histone modifications
Exocytosis
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Summary:Recurrent apnea with intermittent hypoxia (IH) is a major clinical problem in infants born preterm. Carotid body chemo-reflex and catecholamine secretion from adrenal medullary chromaffin cells (AMC) are important for maintenance of cardio-respiratory homeostasis during hypoxia. This article highlights studies on the effects of IH on O2 sensing by the carotid body and AMC in neonatal rodents. Neonatal IH augments hypoxia-evoked carotid body sensory excitation and catecholamine secretion from AMC which are mediated by reactive oxygen species (ROS)-dependent recruitment of endothelin-1 and Ca2+ signaling, respectively. The effects of neonatal IH persist into adulthood. Evidence is emerging that neonatal IH initiates epigenetic mechanisms involving DNA hypermethylation contributing to long-lasting increase in ROS levels. Since adult human subjects born preterm exhibit higher incidence of sleep-disordered breathing and hypertension, DNA hypomethylating agents might offer a novel therapeutic intervention to decrease long-term cardio-respiratory morbidity caused by neonatal IH.
Bibliography:ObjectType-Article-2
SourceType-Scholarly Journals-1
ObjectType-Feature-1
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ISSN:1569-9048
1878-1519
DOI:10.1016/j.resp.2012.07.016