Cerebral erythropoietin promotes sex dependent prevention of disrupted neural control of respiration induced by neonatal stress
Bibliographic record
Abstract
Stress experienced during a critical period of development is a major cause of adult disease (Kivimäki and Steptoe, 2018; Nelson and Gabard‐Durnam, 2020; Shonkoff, 2016; Shonkoff et al., 2009); it has persistent and sex‐specific effects on health and the brain is a major target. One neural system of considerable interest is the neural system regulating breathing. Pathology in this homeostatic control system underlies important clinical disorders such as sleep disordered breathing (SDB). Adult rodents previously subjected to early life stress in the form neonatal maternal separation (NMS) show key features of SDB, including a greater incidence of apneas during sleep and a significant sexual dimorphism. Erythropoietin (EPO) is a potent neuroprotective factor secreted by neurons and astrocytes that prevents stress‐related neurological insults. Because treatment options for SDB are limited, we tested the hypothesis that over expression of neural EPO alleviates NMS‐related respiratory control dysfunction in adult mice. To test this hypothesis, we used a transgenic animal model that selectively overexpress EPO in the brain (Tg21). Mouse pups were raised under standard conditions or subjected to NMS (3h/day; postnatal days 3 to 12). At adulthood, the apnea index and reflexive responses to O 2 (hypoxia) and CO 2 (hypercapnia) were measured using whole body plethysmography; corticosterone levels were measured by ELISA assay. In wild type, NMS augmented apnea frequency in males (not females). This effect of NMS was not observed in Tg21 mice. NMS also caused a sex‐specific increase in basal corticosterone (males only). EPO overexpression reduced this effect. We conclude that overexpression of neural EPO prevents the deleterious impacts of NMS on the development of the stress neuraxis and respiratory control.
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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 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".