ROLE OF ESTRADIOL RECEPTOR BETA (ERβ) ON BRAIN MITOCHONDRIAL FUNCTIONS AND CARDIO‐RESPIRATORY CONTROL IN AGED FEMALE MICE
Bibliographic record
Abstract
We tested the hypothesis that ERβ is involved in brain mitochondrial function and cardio‐respiratory control in aged female mice. We used aged (17–18 months‐old) ERβKO and wild‐type controls (WT) female mice to assess arterial blood pressure (via a tail‐cuff sensor) and indices of respiratory pattern (sighs and apneas – recorded by whole body plethysmography at rest). We also measured respiratory parameters at rest and in response to brief (<10 minutes) exposure to hypoxia (12% O 2 ) or hypercapnia (5% CO 2 ). Because ERβ is localized in mitochondria, and because estradiol and ERβ agonist increase mitochondrial O 2 consumption, we used fresh brain cortex tissue (~2 mg) permeabilized with saponin to assess mitochondrial respiration with high‐resolution respirometry ( O2k‐ Oroboros ) and in‐vitro activity of the complex I of the electron transport chain. In ERβKO female mice, mean arterial blood pressure was lower than in old WT mice (88±4 vs 110±3 mmHg, P<0.05), the frequency of sighs was similar in ERβKO than in WT micez (26±3 vs 19±2 sighs/h P=ns) and the frequency of apneas much lower (4±2 vs 26±9 apnea/h, P=0.01). In ERβKO mice, minute ventilation is reduced in response to hypoxia (−50%, P<0.01) and hypercapnia (−39%, P<0.01) compared to WT mice. Concerning mitochondrial function, with substrates of complex I (Pyruvate/Glutamate/Malate) and in presence of ADP, ERβKO mice have a reduced O 2 consumption compared to WT mice (60±7 vs 98±4 pmol O 2 /s/mg tissue, p<0.05). With the substrate of complex II (succinate) and ADP, there was no difference between ERβKO and WT mice. In vitro activity of complex I is 70% lower in ERβKO mice compared to WT (P<0.01). We conclude that the deletion of ERβ reduces chemoreflex functions and reduces mitochondrial function in the central nervous system. This role ERβ may be relevant in pathological or physiological conditions in which O 2 homeostasis is compromised (sleep apnea, altitude, lung diseases). Support or Funding Information CIHR, Région Rhône Alpes and consulat de France in Québec This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .
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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".