Thyroid hormone deficiency disrupts respiratory control development and responses to hypoxia in newborn rat
Notice bibliographique
Résumé
The brain is an important target of thyroid hormones (THs) at all stage of life, however, the maximal vulnerability to an imbalance of TH supply occurs during the early development when the developing embryo/foetus is dependent on maternal supply of TH. During this time, any maternal TH deficiency, small or severe, can alter brain structure or function which can become progressively and substantially magnified during subsequent developmental periods to produce long‐lasting or permanent deficits. The earlier in development thyroid hormone deficiency occurs, the more profound effects it will have on the development of an organism and individual organs such as brain. There is an abundant literature on the effects of maternal TH deficiency on development and function of the central nervous system, lungs, neuromuscular junctions and diaphragm; however, little is known about this influence on respiratory control development. Because thyroid hormone receptors (TRs) are expressed in the fetal brain during gestation and they are present in the brainstem, we proposed that TH can influence respiratory control development in the newborn rodent. Specifically, we hypothesised that a perinatal deficiency in thyroid hormones is sufficient to disrupt the development of respiratory circuits in the rodent. Thyroid hormone deficiency in the foetus was recreated by administrating an antithyroid susbstance (Methimazole;MMI) in drinking water of the pregnant dam at concentration of 0,02% (weight per volume; w/v) from the first day of pregnancy (gestational day 1; GD1) to the day of experiment with the newborn. In‐vitro and in‐vivo measurements were performed on Sprague Dawley rats aged of 1 and 4 days (P1–P4). Fictive breathing (in‐vitro) was measured by extracting the brainstem with a part of the spinal cord and placing it in a chamber where it was superfused with an artificial cerebrospinal fluid (aCSF). The output signal from the respiratory network was recorded by a suction electrode placed on the fourth ventral root representing the inspiratory signal sent to the diaphragm via the phrenic nerve. Measurements of ventilatory activity (in‐vivo) in newborn pups were performed using whole‐body, flow‐through plethysmography. Development of the hypoxic chemoreflex was compared between groups in each protocol using a 15 minutes period hypoxia. By comparison with controls, pups from MMI treated dams did show age‐dependent decrease in phrenic burst frequency under normoxic conditions. In 4 days old pups (MMI), phrenic burst depression was not observed during hypoxia. The in‐vivo results from the whole‐body plethysmography reveal a decrease in the basal minute ventilation (V E ) in treated 1 day old pups and a blunted hypoxic ventilatory response. We conclude that thyroid deficiency during perinatal period alters the respiratory control development and responsiveness to a hypoxic challenge. Support or Funding Information Supported by NSERC.
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Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,001 |
| Bibliométrie | 0,001 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,001 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».