Pharmacological but not genetically alteration of neural Epo modifies the CO <sub>2</sub> /H <sup>+</sup> central chemosensitivity in postnatal mice at birth
Bibliographic record
Abstract
The central chemosensitivity to CO2/H+ is considered essential for breathing during the maturation of the mammalian respiratory network. In this study we tested the hypothesis that at birth, the neural Epo is involved in the breathing stimulation induced by the activation of central CO2/H+ chemoreceptors. Measurements were performed on newborn Tg21 (overexpressing cerebral Epo), Epo‐TAgh (cerebral Epo deficient mice) and their control (WT‐Tg21 and WT‐Epo‐TAgh) mice aged of 4 day. Fictive breathing (in‐vitro) response to CO2‐induced acidosis or metabolic acidosis 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 (C4) representing the inspiratory signal sent to the diaphragm via the phrenic nerve allowing to determine fictive breathing frequency, amplitude and neural ventilation (Frequency × amplitude). Our results did not show differences between preparations from control and transgenic animals Tg21 and Epo‐TAgh for the fictive breathing frequency and amplitude. However, when Tg21 brainstem preparations were incubated for 1h with sEpoR (the antagosnist of Epo), or with inhibitors of ERK/Akt (thus blocking the activation of the Epo molecular pathway), the fictive breathing response to CO2‐induced acidosis was blunted and showed a significant decrease of the neural ventilation (Tg21‐sEpoR: from 111.7±41.1 to 100.0±20.6; & Tg21‐ERK/Akt inhibitors: from 112.3±20.3 to 100.8±23.8; P<0.05) due to a significant decrease of the amplitude (Tg21‐sEpoR: from 100.0±17.1 to 47.4±11.0; and Tg21‐ERK/Akt inhibitors: from 104.6±10.6 to 54.9±8.4; P<0.05). Our data suggest that the variation of the Epo/sEpoR ratio is central in the breathing modulation, and open up clinical perspectives based on the use of Epo drugs at birth in hypoventilation cases. Support or Funding Information Founded by FRQS, Région Rhône‐Alpes and consulat de France à Québec
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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 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".