Erythropoietin impacts the stress‐related respiratory dysfunction in mice: neonatal maternal separation and sex dimorphism
Bibliographic record
Abstract
Neonatal maternal separation (NMS) is an established model of early life adversity that mimics stressful conditions experienced by newborn and infants. NMS disrupts brain development and as adults, individuals show sex‐dependent abnormal neuroendocrine response, predisposing them to physiological/psychological disorders. Concerning the neural control of respiration, studies in rats revealed that NMS causes respiratory instability and increased levels of corticosterone that remained during adulthood. Moreover, increased ventilatory response to hypoxia (HVR) but decreased to hypercapnia (HcVR) was observed in male animals, while decreased HVR but increased HcVR was observed in female rats. Although it is primarily recognized for its capacity to stimulate erythrocyte production, erythropoietin (Epo) is a cytokine that is also produced in the brain (by neurons and astrocytes), and plays role in development, maintenance, protection and repair of the nervous system. Studies from our lab demonstrated that cerebral Epo is a potent and sex‐specific respiratory stimulant that enhances the ability to tolerate hypoxic conditions at neonatal and adult ages. As cerebral Epo also attenuates the activation of the hypothalamic‐pituitary‐adrenal (HPA) axis, here we hypothesized that Epo protects against the stress‐induced cardio‐respiratory dysfunction produced by NMS. To test this hypothesis, circulating corticosterone level of adult (3 months) male and female Tg21 mice, was increased by subcutaneous implantation of beeswax pellets. 14 days later basal ventilation, HVR (10%O 2 in N 2 ) and HcVR (5% CO 2 , 21%O 2 in N 2 ) was evaluated by whole‐body plethysmography. Our preliminary results showed that corticosterone does not alter basal ventilation nor HVR in female and male Tg21 mice. However, corticosterone decreased HcVR in female Tg21 mice, meanwhile males showed an increased HcVR. These results suggest that Epo modulates the cortiscosterone‐induced cardiorespiratory dysfunctions. Support or Funding Information Canadian Institutes of HealthResearch (MOP 130258), the Star Foundation for Children's HealthResearch. The salary of Jorge Soliz is supported by the “Fonds de recherche du Quebec‐Santé” (FRQ‐S).
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| 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".