Disruption of estradiol regulation of orexin neurons: a novel mechanism in excessive ventilatory response to CO2 inhalation in a female rat model of panic disorder
Bibliographic record
Abstract
Abstract Panic disorder (PD) is ~2 times more frequent in women. An excessive ventilatory response to CO 2 inhalation is more likely during the premenstrual phase. While ovarian hormones appear important in the pathophysiology of PD, their role remains poorly understood as female animals are rarely used in pre-clinical studies. Using neonatal maternal separation (NMS) to induce a “PD-like” respiratory phenotype, we tested the hypothesis that NMS disrupts hormonal regulation of the ventilatory response to CO 2 in female rats. We then determined whether NMS attenuates the inhibitory actions of 17-β estradiol (E 2 ) on orexin neurons (ORX). Pups were exposed to NMS (3 h/day; postnatal day 3–12). The ventilatory response to CO 2 -inhalation was tested before puberty, across the estrus cycle, and following ovariectomy. Plasma E 2 and hypothalamic ORX A were measured. The effect of an ORX 1 antagonist (SB334867; 15 mg/kg) on the CO 2 response was tested. Excitatory postsynaptic currents (EPSCs) were recorded from ORX neurons using whole-cell patch-clamp. NMS-related increase in the CO 2 response was observed only when ovaries were functional; the largest ventilation was observed during proestrus. SB334867 blocked this effect. NMS augmented levels of ORX A in hypothalamus extracts. EPSC frequency varied according to basal plasma E 2 levels across the estrus cycle in controls but not NMS. NMS reproduces developmental and cyclic changes of respiratory manifestations of PD. NMS disrupts the inhibitory actions of E 2 on the respiratory network. Impaired E 2 -related inhibition of ORX neurons during proestrus is a novel mechanism in respiratory manifestations of PD in females.
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 distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| 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 | 0.001 |
| 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) | 0.000 | 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 teacher head, 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".