Paraventricular nucleus neurons: important regulators of respiratory movement in mice with chronic intermittent hypoxia.

OBJECTIVE

Obstructive sleep apnea-hypopnea syndrome (OSAHS) is a prevalent respiratory disorder. Chronic intermittent hypoxia (CIH) is a key pathophysiological change linked to the development of OSAHS. The paraventricular hypothalamic nucleus (PVN) plays a role in respiratory control. This study aimed to explore a novel treatment for OSAHS through PVN stimulation.

METHOD: The Cre/LoxP gene expression strategy, along with the viral tracer technique and immunofluorescence staining, was employed to confirm the anatomical relationship between the PVN and the preBötzinger complex (preBötC) in mice. A CIH mouse model was established, and chemogenetics was integrated with whole-body plethysmography (WBP) to monitor the respiratory function changes in CIH mice.

RESULT: (1) A notably higher density of c-Fos-positive neurons was detected in the PVN of CIH mice compared to normoxic mice (p < 0.0001). (2) Neuronal somata and nerve fibers that were co-labeled were found in both the PVN and preBötC. (3) Modulating PVN neurons through chemogenetic methods affected respiratory frequency (RF) and minute ventilation (MV) in CIH mice, with tidal volume (TV) remaining unchanged. Furthermore, the activation of PVN neurons increased c-Fos expression in the preBötC.

CONCLUSION

A direct relationship exists between the PVN and preBötC. CIH increased c-Fos expression in respiratory-related nuclei, including the PVN. Modulating the PVN activity impacts MV by adjusting the RF; without influencing arterial blood gas levels. The PVN is probably involved in respiratory control via the PVN-preBötC circuit.