Gestational stress promotes pathological apneas and sex-specific disruption of respiratory control development in newborn rat.

TitleGestational stress promotes pathological apneas and sex-specific disruption of respiratory control development in newborn rat.
Publication TypeJournal Article
Year of Publication2013
AuthorsFournier, S, Steele, S, Julien, C, Fournier, S, Gulemetova, R, Caravagna, C, Soliz, J, Bairam, A, Kinkead, R
JournalJ Neurosci
Volume33
Issue2
Pagination563-73
Date Published2013 Jan 09
ISSN1529-2401
Keywords8-Hydroxy-2-(di-n-propylamino)tetralin, Animals, Animals, Newborn, Apnea, Corticosterone, Female, Hypercapnia, Hypoxia, Male, Oxygen Consumption, Plethysmography, Pregnancy, Pregnancy, Animal, Rats, Respiratory Mechanics, Respiratory Physiological Phenomena, Serotonergic Neurons, Serotonin, Serotonin Receptor Agonists, Sex Characteristics, Stress, Psychological, Testosterone
Abstract

Recurrent apneas are important causes of hospitalization and morbidity in newborns. Gestational stress (GS) compromises fetal brain development. Maternal stress and anxiety during gestation are linked to respiratory disorders in newborns; however, the mechanisms remain unknown. Here, we tested the hypothesis that repeated activation of the neuroendocrine response to stress during gestation is sufficient to disrupt the development of respiratory control and augment the occurrence of apneas in newborn rats. Pregnant dams were displaced and exposed to predator odor from days 9 to 19 of gestation. Control dams were undisturbed. Experiments were performed on male and female rats aged between 0 and 4 d old. Apnea frequency decreased with age but was consistently higher in stressed pups than controls. At day 4, GS augmented the proportion of apneas with O(2) desaturations by 12%. During acute hypoxia (12% O(2)), the reflexive increase in breathing augmented with age; however, this response was lower in stressed pups. Instability of respiratory rhythm recorded from medullary preparations decreased with age but was higher in stressed pups than controls. GS reduced medullary serotonin (5-HT) levels in newborn pups by 32%. Bath application of 5-HT and injection of 8-OH-DPAT [(±)-8-hydroxy-2-di-(n-propylamino) tetralin hydrobromide; 5-HT(1A) agonist; in vivo] reduced respiratory instability and apneas; these effects were greater in stressed pups than controls. Sex-specific effects were observed. We conclude that activation of the stress response during gestation is sufficient to disrupt respiratory control development and promote pathological apneas in newborn rats. A deficit in medullary 5-HT contributes to these effects.

DOI10.1523/JNEUROSCI.1214-12.2013
Alternate JournalJ. Neurosci.
PubMed ID23303936
Grant ListMOP 119272 / / Canadian Institutes of Health Research / Canada
MOP 119337 / / Canadian Institutes of Health Research / Canada