Thyroid hormones during the perinatal period are necessary to respiratory network development of newborn rats.

TitleThyroid hormones during the perinatal period are necessary to respiratory network development of newborn rats.
Publication TypeJournal Article
Year of Publication2021
AuthorsRousseau, J-P, Tenorio-Lopes, L, Ghio, SCortez, Desjardins, P, Fournier, S, Kinkead, R
JournalExp Neurol
Volume345
Pagination113813
Date Published2021 11
ISSN1090-2430
KeywordsAnimals, Animals, Newborn, Antithyroid Agents, Female, GABA-A Receptor Antagonists, Male, Methimazole, Nerve Net, Phrenic Nerve, Plethysmography, Pregnancy, Rats, Rats, Sprague-Dawley, Respiration, Respiratory Mechanics, Thyroid Hormones
Abstract

Thyroid hormones (THs) are essential for foetal brain development. Because the gestating mother is the main source of THs to the foetus, maternal hypothyroidism and/or premature birth compromise neurological outcomes in the offspring. Respiratory instability and recurrent apneas due to immaturity of the respiratory control network are major causes of morbidity in infants. Inadequate TH supply may be sufficient to delay perinatal maturation of the respiratory control system; however, this hypothesis remains untested. To address this issue, maternal hypothyroidism was induced by adding methimazole (MMI; 0.02% w/v) to the drinking water of pregnant dams from conception to postpartum day 4 (P4). The effect of TH supplementation on respiratory function was tested by injecting levothyroxine (L-T4) in newborns at P1. Respiratory function was assessed by plethysmography (in vivo) and recording of phrenic output from medullary preparations (in vitro). By comparison with controls, TH deficiency increased the frequency of apneas and decreased basal ventilation in vivo and prevented the age-dependent increase in phrenic burst frequency normally observed in vitro. The effects of TH deficiency on GABAergic modulation of respiratory activity were measured by bath application of muscimol (GABA agonist) or bicuculline (GABA antagonist). The phrenic burst frequency responses to GABAergic agents were consistently greater in preparations from TH deficient pups. L-T4 supplementation reversed part of the respiratory anomalies related to MMI treatment in vitro. We conclude that TH deficiency during the perinatal period is sufficient to delay maturation of the respiratory control network development. Excessive GABAergic inhibition may contribute to this effect.

DOI10.1016/j.expneurol.2021.113813
Alternate JournalExp Neurol
PubMed ID34284029