Thyroid hormone deficiency potentiates GABAergic inhibition of the brainstem respiratory network in newborn rat
Bibliographic record
Abstract
Because thyroid hormones (THs) are present in the brainstem and are essential for both the differentiation of the presynaptic GABAergic neurons and the maturation of the postsynaptic components of the GABAergic system, we proposed that TH deficiency during gestation is sufficient to disrupt GABAergic modulation of the brainstem's respiratory network in newborn rats. 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 measurements were performed on Sprague Dawley rats aged of 4 days. 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. Compared to controls, pups from MMI treated dams showed 69% decreased phrenic burst frequency under baseline conditions (5.5 ± 0.4 vs 8.0 ± 0.4 bursts/min; treatment effect: P=0.0003). Moreover, they presented an increased dose‐dependent depression of fictive breathing following Muscimol application (GABA A receptor agonist) (dose 0.1μM: −27 ± 7.9 vs −7.8 ± 3.4 % change from baseline; treatment effect: P=0.0233) and increased elevation of phrenic burst frequency following Bicuculline exposure (GABA A receptor antagonist) (dose 8μM: 25.4 ± 5.3 vs 5.3 ± 3.9 % change from baseline; treatment effect P=0.0085). This treatment‐dependent augmentation of GABAergic tone did not affect burst amplitude, thus indicating that the role of TH on GABAergic modulation is selective. We conclude that TH deficiency results in an increased GABAergic inhibition in the core elements of the respiratory control circuit which could explain the reduced phrenic bursts frequency observed in the treated pups. These results provide new hypotheses regarding the origins of respiratory disorders of the newborn involving reduced respiratory drive such as apnea of prematurity. Support or Funding Information Supported by NSERC.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 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".