Details

Autor(en) / Beteiligte

• Gama de Barcellos Filho, Procopio
• Dantzler, Heather A.
• Hasser, Eileen M.
• Kline, David D.

Titel

Oxytocin and corticotropin‐releasing hormone exaggerate nucleus tractus solitarii neuronal and synaptic activity following chronic intermittent hypoxia

Ist Teil von

• The Journal of physiology, 2024-07, Vol.602 (14), p.3375-3400

Ort / Verlag

England: Wiley Subscription Services, Inc

Erscheinungsjahr

2024

Quelle

Wiley Online Library - AutoHoldings Journals

Beschreibungen/Notizen

• Chronic intermittent hypoxia (CIH) in rodents mimics the hypoxia‐induced elevation of blood pressure seen in individuals experiencing episodic breathing. The brainstem nucleus tractus solitarii (nTS) is the first site of visceral sensory afferent integration, and thus is critical for cardiorespiratory homeostasis and its adaptation during a variety of stressors. In addition, the paraventricular nucleus of the hypothalamus (PVN), in part through its nTS projections that contain oxytocin (OT) and/or corticotropin‐releasing hormone (CRH), contributes to cardiorespiratory regulation. Within the nTS, these PVN‐derived neuropeptides alter nTS activity and the cardiorespiratory response to hypoxia. Nevertheless, their contribution to nTS activity after CIH is not fully understood. We hypothesized that OT and CRH would increase nTS activity to a greater extent following CIH, and co‐activation of OT+CRH receptors would further magnify nTS activity. Our data show that compared to their normoxic controls, 10 days’ CIH exaggerated nTS discharge, excitatory synaptic currents and Ca2+ influx in response to CRH, which were further enhanced by the addition of OT. CIH increased the tonic functional contribution of CRH receptors, which occurred with elevation of mRNA and protein. Together, our data demonstrate that intermittent hypoxia exaggerates the expression and function of neuropeptides on nTS activity. Key points Episodic breathing and chronic intermittent hypoxia (CIH) are associated with autonomic dysregulation, including elevated sympathetic nervous system activity. Altered nucleus tractus solitarii (nTS) activity contributes to this response. Neurons originating in the paraventricular nucleus (PVN), including those containing oxytocin (OT) and corticotropin‐releasing hormone (CRH), project to the nTS, and modulate the cardiorespiratory system. Their role in CIH is unknown. In this study, we focused on OT and CRH individually and together on nTS activity from rats exposed to either CIH or normoxia control. We show that after CIH, CRH alone and with OT increased to a greater extent overall nTS discharge, neuronal calcium influx, synaptic transmission to second‐order nTS neurons, and OT and CRH receptor expression. These results provide insights into the underlying circuits and mechanisms contributing to autonomic dysfunction during periods of episodic breathing. figure legend Following chronic intermittent hypoxia (CIH), the augmentation in neuronal activity and synaptic transmission by oxytocin (OT) and corticotropin‐releasing hormone (CRH) within the nucleus tractus solitarii (nTS) was enhanced compared to normoxia exposure. nTS slices were analysed to assess neuronal electrophysiological properties and calcium (Ca2+) influx. CIH exaggerated nTS discharge, excitatory synaptic currents and Ca2+ influx specifically in response to CRH, with further amplification observed upon the addition of OT. CIH also increased the tonic functional contribution of CRH and OT receptors to synaptic activity and was accompanied by elevations in mRNA. Together, CIH exaggerates the function of OT and CRH within the nTS, contributing to respiratory and cardiovascular dysregulation in conditions like obstructive sleep apnoea.