Sex-Specific Consequences of Neonatal Stress on Cardio-Respiratory Inhibition Following Laryngeal Stimulation in Rat Pups.

TitleSex-Specific Consequences of Neonatal Stress on Cardio-Respiratory Inhibition Following Laryngeal Stimulation in Rat Pups.
Publication TypeJournal Article
Year of Publication2017
AuthorsBaldy, C, Chamberland, S, Fournier, S, Kinkead, R
JournaleNeuro
Volume4
Issue6
Date Published2017 Nov-Dec
ISSN2373-2822
Abstract

The presence of liquid near the larynx of immature mammals triggers prolonged apneas with significant O desaturations and bradycardias. When excessive, this reflex (the laryngeal chemoreflex; LCR) can be fatal. Our understanding of the origins of abnormal LCR are limited; however, perinatal stress and male sex are risk factors for cardio-respiratory failure in infants. Because exposure to stress during early life has deleterious and sex-specific consequences on brain development it is plausible that respiratory reflexes are vulnerable to neuroendocrine dysfunction. To address this issue, we tested the hypothesis that neonatal maternal separation (NMS) is sufficient to exacerbate LCR-induced cardio-respiratory inhibition in anesthetized rat pups. Stressed pups were separated from their mother 3 h/d from postnatal days 3 to 12. At P14-P15, pups were instrumented to monitor breathing, O saturation (So), and heart rate. The LCR was activated by water injections near the larynx (10 ┬Ál). LCR-induced apneas were longer in stressed pups than controls; O desaturations and bradycardias were more profound, especially in males. NMS increased the frequency and amplitude of spontaneous EPSCs (sEPSCs) in the dorsal motor nucleus of the vagus (DMNV) of males but not females. The positive relationship between corticosterone and testosterone observed in stressed pups (males only) suggests that disruption of neuroendocrine function by stress is key to sex-based differences in abnormal LCR. Because testosterone application onto medullary slices augments EPSC amplitude only in males, we propose that testosterone-mediated enhancement of synaptic connectivity within the DMNV contributes to the male bias in cardio-respiratory inhibition following LCR activation in stressed pups.

DOI10.1523/ENEURO.0393-17.2017
Alternate JournaleNeuro
PubMed ID29308430
PubMed Central IDPMC5753062