Mitochondrial‐targeted antioxidant drugsas therapeutically tools for apnea of prematurity: intermittent hypoxia and sex dimorphism
Bibliographic record
Abstract
Immaturity of the brainstem network system that controls breathing leads to apnea of prematurity (AoP). While AoP is a developmental (and thus self‐resolving) disorder, it is not the apnea but the associated decrease of arterial oxygen levels (Intermittent Hypoxemia ‐ IH) what is detrimental for neural maturation. IH induces mitochondrial dysfunction, increased production of reactive oxygen species (ROS), and oxidative stress, thus promoting higher breathing instability, delayed neural maturation and prolonged hospitalization. We hypothesized that the mitochondrial‐targeted antioxidant drug MitoTEMPO, by restoring mitochondrial dysfunction, protects newborns against the consequences of IH induced by AoP. Moreover, keeping in mind that male sex is an important risk factor for several respiratory diseases in preterm neonates experiments were performed in male and female newborn rats exposed to IH during postnatal days (P) 3–10. During this time, animals were daily injected (i.p.) with vehicle or MitoTEMPO (10–12 pups/group). At P10 the frequency of apneas at rest were measured (as an index of respiratory dysfunction) by plethysmography. Next, the cortex tissue was collected, and a high‐resolution Oxygraph‐2k was used to evaluate the mitochondrial bioenergetics and ROS (H 2 O 2 ) production using saponin‐permeabilized tissue punches of 1.5–3 mg weight. Our preliminary results obtained in male animals showed that mitoTEMPO: 1) restored the IH‐mediated increase of apneic events, 2) restored the IH‐mediated decrease of mitochondrial respiration of complex I (NADH‐linked respiration), and complex II (FADH2‐linked respiration), and 3) decreased the IH‐mediated increase of mitochondrial H 2 O 2 . Surprisingly, no impact of IH and/or the treatment with mitoTEMPO was observed in female animals. We conclude that neonatal IH leads to respiratory disturbances in male animals only. Moreover, our results suggest that antioxidant drugs may be used as new therapeutical tools for apnea of prematurity in males. Support or Funding Information Jorge Soliz is funded by the Canadian Institutes of Health Research (CIHR – Catalyst grant sex as a variable in biomedical research‐IC118777). The salary of Jorge Soliz is supported by Laval University. The Canadian Foundation for Innovations (FCI – 32986) supported the acquisition of state‐of‐the art equipment in Jorge Soliz lab. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .
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 | 0.000 |
| 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".