Sex-Specific Effects of Neonatal Stress on Brainstem Expression of Orexin1-Receptors
Notice bibliographique
Résumé
Introduction and hypothesis: Located within the hypothalamus, orexin-producing neurons (ORX) regulate arousal, feeding, and cardiorespiratory function. Panic disorders (PD) affects ~5% of the North American population. Stress-related “hyperactivation” of the ORX system is a leading hypothesis to explain the pathophysiology of PD. One important sub-group of PD patients show significant respiratory symptoms, including an excessive ventilatory response to CO 2 inhalation. Manifestations of PD are sex-specific: the prevalence of PD is ~2 times higher in women compared to men and the intensity of the ventilatory response to CO 2 fluctuates with the hormonal cycle. Early life stress is a risk factor for PD and we recently demonstrated that in rats, neonatal maternal separation (NMS) augments the ventilatory response to CO 2 (5%; 10 min) of adult females (but not males); this effect peaks with the rise of 17-b estradiol (E 2 ) during proestrus. Because NMS-related enhancement of the hyperventilatory response to CO 2 can be prevented by a selective ORX1-antagonist, we tested the hypothesis that sex, hormonal status and NMS interact to influence the expression of ORX-1 receptors in brainstem regions that regulate breathing. Methods: Following birth, pups were either exposed to NMS (3h/day from postnatal days 3 to 12) or raised under standard conditions. Rats were then raised until adulthood (8 weeks); experiments were performed on males, females in proestrus (high E 2 ), and ovariectomised (low E 2 ) females (2 weeks post-surgery). We used in situ hybridization histochemistry to quantify the expression of mRNA for ORX-1 receptors. The ORX-1 receptors signal was revealed by autoradiography emulsion and slides were examined under darkfield microscopy. Expression of ORX-1 receptors was quantified by measuring the pixel density of the hybridization signal in selected brainstem regions that regulate CO 2 response. Results: The locus coeruleus (LC) contained the highest expression of ORX-1 receptors amongst the structures studied. In males, NMS was associated with significant decreases in ORX-1 expression in the LC and nucleus of the solitary tract (NTS). By comparison with OVX females, proestrus augmented ORX-1 expression in the LC of controls, but not NMS. By comparison with OVX, proestrus augmented ORX-1 expression in the raphe obscurus, especially in NMS females. Expression of ORX-1 was unchanged in the NTS of females. Conclusion and perspectives: We conclude that sex and the female’s hormonal status are important determinants of ORX-1 expression and that NMS can alter these relationships; however, those effects are structure-specific. In light of the evidence indicating that 5-HT dysfunction contributes to PD, the results observed in the raphe obscurus point to a plausible mechanism. This study was supported by ‘the Québec Heart and Lung Institute Research Foundation’. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| 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 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 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 tête enseignante, 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 ».