Neonatal stress and loss of ovarian hormones: a novel multidisciplinary approach to understand the coincidence of cardiorespiratory and metabolic disorders in females
Notice bibliographique
Résumé
Introduction In women, the prevalence of sleep apnea (SA) rises 3‐fold at menopause and most patients also present hypertension and obesity. While the “protective effects” of ovarian hormones are well documented, we do not know why the loss of ovarian hormones leads to SA and related cardiovascular and metabolic disorders only in a subpopulation of women. Because neonatal stress is a major cause of adult diseases, we tested the hypothesis that loss of ovarian function reveals the latent effects of stress on cardiorespiratory and metabolic control. To do so, we subjected female rats to neonatal maternal separation (NMS), a translational model of early life stress. Methodology Rat pups subjected to NMS were placed in a temperature‐controlled incubator 3h/day from postnatal day 3 to 12; controls (CTRL) were undisturbed. The effects of loss of ovarian function were tested using a surgical approach (ovariectomy; OVX, animals with 8 weeks old) and aging (40 weeks old). Measurements of ventilation (by whole body plethysmography), blood pressure (by tail cuff plethysmography), and body composition (by nuclear magnetic resonance) were made. We also harvested brains from 8 weeks old females (SHAM versus OVX). Then, we compared the expression of FosB, a transcription factor that indicates neuronal activity. The number of FosB expressing neurons was counted in the paraventricular nucleus of the hypothalamus (PVH), the main structure regulating the hypothalamic pituitary adrenal (HPA) axis. Results NMS does not affect the incidence of apneic events in all groups. At 8 weeks, mean arterial pressure (MAP) of NMS females was 5% lower than CTRL. In addition, NMS females had 10% more body mass compared to CTRL. At 40 weeks, the MAP of NMS females was 15% higher than CTRL. In both ages, NMS presented 4% more fat, and 4% less lean tissue. OVX did not affect cardiorespiratory function but augmented the number of neurons expressing FosB in the PVH by 55% in NMS, not in CTRL females. Discussion The hypotension observed in young (8 weeks) NMS females was unexpected but is consistent with the fact that hypotension is a common comorbidity of depression. PVH dysfunction contributes to the increase of sympathetic vasomotor activity, characteristic of multiple forms of hypertension. Additionally, the chronic activation of the HPA axis can leads to obesity. The increased expression of FosB in OVX NMS animals indicate that ovarian hormones prevents the stress‐related rise of activity of the HPA axis. At 40 weeks old, the fact that NMS animals were obese and hypertensive indicates that those effects are age dependent. The emergence of dysregulation on the stress neuroaxis is a plausible mechanism to explain those results. Together, these data indicate that neonatal stress may explain why a subpopulation of women are at risk of developing cardiorespiratory and metabolic disturbance at menopause. Ongoing experiments will evaluate the incidence of SA in older animals (60 weeks old) and exploring the underlying mechanisms.
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Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,001 |
| Science ouverte | 0,000 | 0,001 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».