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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.