Estradiol Receptor Agonists α and β Protect Against Brain Mitochondrial Dysfunction in a Model of Sleep Apnea
Bibliographic record
Abstract
We tested the hypothesis that intermittent hypoxia (IH) induces a mitochondrial dysfunction in the brain of adult female rats, and that agonists of α and β estradiol receptors (ER) protect against this effect. Female rats were ovariectomized (OVX) and implanted with an osmotic pump continuously delivering vehicle (OVX‐Veh), PPT (OVX‐PPT – ERα agonist ‐ 30μg/kg/day) or DPN (OVX‐DPN ‐ ERβ agonist ‐ 100μg/kg/day). Two weeks later, the animals were exposed to intermittent hypoxia (IH‐21–10% O 2 – 10 cycles/hour – 8 hours/day – 7 days) or room air (RA). We then used fresh brain cortex tissue (~2 mg) permeabilized with saponin to assess mitochondrial functions with high‐resolution respirometry ( O2k‐Oroboros ). With substrates of complex I (Pyruvate/Glutamate/Malate) and in presence of ADP, rats exposed to IH have a reduced O 2 consumption compared to RA rats (55±7 vs 88±4 pmol O 2 /s/mg tissue, p<0.0001). PPT and DPN treatments prevented this alteration (O 2 consumption being respectively 104±6 and 90±6 pmolO 2 /s/mg, p<0.0001 vs OVX‐IH rats). With the substrate of complex II (succinate) and ADP, there was no effect of IH, but O 2 consumption was higher in OVX‐PPT rats compared to OVX‐IH rats. With the substrates of complexes I+II and ADP, O 2 consumption was reduced by IH exposure compared to RA (51±9 vs 87±12 pmol O 2 /s/mg, p<0.0001), and this was partially prevented by DPN (68±10, p<0.03 vs OVX‐IH), while OVX‐PPT rats had the highest O 2 consumption (125±11 pmolO 2 /s/mg, p<0.0001 vs OVX‐IH and OVX‐RA). H 2 O 2 production measured by fluorometry with the substrates of complexes I+II and ADP is increased by exposure to IH compared to RA (3.2 ±0.4 vs 0.9±0.3 pmol H 2 O 2 /min/mg– p=0.002), and this is prevented by DPN and PPT (1.8 ±0.2 vs 1.6±0.2 pmol H 2 O 2 /min/mg). We conclude that in OVX female rats, IH impairs the mitochondrial respiratory chain through the complex I leading to an increase of ROS (H 2 O 2 ) production. Selective agonists of ERα and ERβ prevent the mitochondrial dysfunction. ERα appears more efficient to increase mitochondrial respiratory function in this model. This opens new perspectives for menopausal women suffering of sleep apnea. Support or Funding Information Founded by CIHR, 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 | 0.000 |
| 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".