Thyroid hormone deficiency disrupts respiratory control development and responses to hypoxia in newborn rat
Bibliographic record
Abstract
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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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".