Neonatal stress augments the hypoxic chemoreflex of adult male rats by increasing AMPA receptor‐mediated modulation
Notice bibliographique
Résumé
New Findings What is the central question of this study? Early life exposure to stress augments the hypoxic chemoreflex of adult male rats. This effect predisposes to respiratory instability during sleep. We used pharmacological and neuroanatomical approaches to determine whether a change in glutamatergic neurotransmission contributes to this abnormal respiratory phenotype. What is the main finding and its importance? We initially showed that neonatal stress augments sensitivity to an AMPA/kainate receptor antagonist. Results from autoradiography experiments support this observation because they demonstrate that neonatal stress increases expression of AMPA receptors in key regions that regulate breathing. Region‐specific changes in brain‐derived neurotrophic factor expression may contribute to these changes in glutamatergic neurotransmission. These results bring new insight into the pathophysiology of sleep‐disordered breathing. Neonatal stress disrupts the developmental trajectory of homeostatic systems. Adult (8‐ to 10‐week‐old) male rats exposed to maternal separation (a form of neonatal stress) display several traits reported in patients suffering from sleep‐disordered breathing, including an augmented hypoxic chemoreflex. To understand the mechanisms behind this effect, we tested the hypothesis that neonatal stress augments glutamatergic neurotransmission in three regions involved in respiratory regulation, namely the nucleus of the solitary tract, the paraventricular nucleus of the hypothalamus and the phrenic motor nucleus. Maternal separation was performed for 3 h day −1 from postnatal day 3 to 12. Control pups were undisturbed. Adult rats were instrumented for intracerebroventricular injection of the AMPA/kainate receptor antagonist CNQX (0–4.3 μ m ). Using plethysmography, ventilatory activity was measured at rest in awake animals during normoxia (fractional inspired O 2 = 0.21) and during acute hypoxia (fractional inspired O 2 = 0.12; 20 min). Following vehicle injection, the hypoxic ventilatory response of stressed rats was 35% greater than that of controls. Microinjection of CNQX attenuated the hypoxic ventilatory response, but the effect observed in stressed rats was greater than that in control animals. Autoradiography experiments showed that neonatal stress augments expression of AMPA receptors within the paraventricular nucleus of the hypothalamus and the phrenic motor nucleus. Quantification of brain‐derived neurotrophic factor showed that neonatal stress augments brain‐derived neurotrophic factor expression only within the paraventricular nucleus. We conclude that neonatal stress augments the hypoxic chemoreflex by increasing the efficacy of glutamatergic synaptic inputs projecting onto key respiratory structures, especially the paraventricular nucleus of the hypothalamus. These data provide new insight into the aetiology of sleep‐disordered breathing.
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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) | 0,001 | 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 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 ».