Stress-induce reduction of hypoglossal motoneuron excitability in male rats: a novel mechanism in the pathophysiology of obstructive sleep apnea (OSA)

Obstructive sleep apnea (OSA) is a multifactorial respiratory disorder affecting nearly 1 billon of adults worldwide. Anomalies in respiratory control during sleep contribute to airway obstructions and recurrent desaturations; however, the origins of the problem are not well known. Stress disrupts brain function and increases the risk of OSA co-morbidities, including hypertension and obesity; recent in vivo experiments in urethane anesthetised rats indicate that stress augments the frequency of obstructive events with O 2 desaturations during “sleep-like” states. Because stress-related reduction in genioglossus function emerged as an important mechanism, we tested the hypothesis that acute stress reduces excitability of hypoglossal motoneurons using whole cell recording. Adult male rats (52 – 60 days old) were anesthetised (isoflurane, 3% in air) and hypoglossal motoneurons were retrogradely labeled by intralingual injection of 10µl of dextran tetramethylrhodamine in the genioglossus. On the day before the experiments, rats were either subjected to a 90 min session of immobilisation stress (n = 11) or handled briefly by the experimenter (n = 15). Rats were then anesthetised (isoflurane) before brains were harvested and sectioned (250 µM) for whole cell recording in current clamp. Stress did not affect Vm or membrane capacitance but augmented rheobase (49%; p = 0.04) and action potential threshold (15%, p = 0.003). Stress also reduced the firing frequency response to step current injections (p < 0.001). We conclude that, independently of other comorbidities such as obesity, acute stress alone reduces hypoglossal motoneuron excitability. These data indicate that stress is an important factor in the etiology of OSA. Supported by the Canadian Institutes of Health Research and the Foundation of the Québec Heart & Lung Institute. 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.