Effects of aging and CIH exposure on respiratory function, postsynaptic excitatory muscarinic receptor expression, and cholinergic inputs
Notice bibliographique
Résumé
Alzheimer’s disease (AD) is an irreversible neurodegenerative process that is often comorbid with several diseases, including Obstructive Sleep Apnea (OSA). An individual with AD is 5 times more likely to have OSA than a non-AD individual of similar age. OSA is characterized by partial or complete occlusion of the upper airways, occurring intermittently throughout sleep, leading to arterial blood desaturation of oxygen and sleep fragmentation. Persistent intermittent airway occlusion during sleep that results in blood oxygen desaturation is termed Chronic Intermittent Hypoxia (CIH). A contributing factor to OSA is insufficient neural control of upper airway muscles, particularly the tongue, innervated by hypoglossal motoneurons (XII MNs). We hypothesize that CIH exposure will change respiratory patterns in adult mice and that these effects will be more pronounced in older adult mice. As an initial test of our hypothesis, we have examined the effects of CIH on respiratory pattern in three-month old adult mice. For each day of the protocol, mice were subjected to 8 hours of intermittent hypoxia with a nadir of 5% oxygen for 15 s and a recovery at 21% oxygen for 4 minutes and 45 seconds. Ramp times to go between 5% and 21% oxygen were just over one minute. Thus, mice were exposed to ~60 hypoxic episodes/8-hour period. Respiratory parameters were collected using whole body plethysmography at day 0 (i.e., before any exposure to intermittent hypoxia) and then after 4 and 7 days of intermittent hypoxia exposure. Respiratory parameters collected include: tidal volume (Vt), respiratory frequency (fR), and minute ventilation (Ve). At the end of the CIH protocol, brain tissue was collected for future immunofluorescence and molecular analysis. Our preliminary data evaluated respiratory function of young mature male CD1 mice (n=3) in response to CIH over 7 days and are reported as mean (range). Our preliminary data indicated a trend for a transient decrease in Vt and Ve and a transient increase in fR after four days of CIH exposure compared to baseline or after seven days of CIH exposure. Vt (mL) for days 0, 4, and 7 was 14.2 (11.96-18.25), 11.6 (8.80-13.01), and 15.3 (12.05-21.52), respectively. fR (breath/min) for days 0, 4, and 7 was 208 (140-253), 217 (133-266), and 207 (152-278) respectively. Ve (mL/min, kg) at days 0, 4, and 7 was 2821.7 (2563.25-3117.28), 2449.2 (1728.48-3413.09), and 3010.9 (2375.00-3370.12), respectively. Further data collection will be needed to determine whether this trend continues and additional data collection to evaluate metabolic rate will be needed to determine the functional effects of CIH on respiratory parameters in adult mice. Finally, we will repeat these experiments in older adult mice to evaluate whether CIH has an age-dependent effect on respiratory function. Funding from the Arizona Alzheimer's Consortium Development Grant (to ALR and GSFS and DBZ) and Midwestern University Kenneth A. Suarez Summer Research Fellowship (to JMH) This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board 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 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 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| 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 ».