Distribution of leptin receptors in the brain stem: possible route in the pathophysiology of neuromuscular control of airway resistance during sleep

Introduction: Leptin, a hormone related to satiety, has been studied because of its association with obesity and sleep apnea. The distribution of leptin receptors in the brain stem, and in the hypoglossal nucleus, has not yet been described. The stimulation of these muscles has been studied in the treatment of sleep apnea. Objective: to detail the presence of leptin receptors in the nuclei of these nerves to enable studies of stimulation of this region through leptin. Methods: the brains of five cadavers, removed during necropsy, collected at the Death Verification Service were included. An informed consent was signed by a family member (wife, mother or son/daughter) who answered specific questionnaire concerning comorbities. Anthropometric measurements were recorded. The medulla oblongata and pons fragments were identified. Immunohistochemical staining analysis was performed to identify the location of the leptin receptors. Results: In the immunohistochemical analysis an intense staining signal of the brownish coloration of neurons was evidenced in the hypoglossal nerve nucleus, moderate in the olivary nucleus and mild in the dorsal nucleus of the vagus and trigeminal nucleus. In motor neurons, more intense brown pigmentation can be observed in the nucleus and cytoplasm when compared to sensory neurons. Conclusion: The immunoexpression of leptin receptor was demonstrated in the motor neurons of the human hypoglossal nucleus. These results may contribute to unravel details of the pathophysiology of neuromuscular control of airway collapse during sleep and to the development of new drugs capable of improving the neuromuscular tone of upper airway in apneic individuals. (c) 2022 Elsevier B.V. All rights reserved.

Automated summary

This study aimed to investigate the distribution of leptin receptors in the brain stem and hypoglossal nucleus, and their association with sleep apnea. Immunohistochemical staining analysis was conducted on five cadavers, revealing the immunopositivity of leptin receptors in the motor neurons of the hypoglossal nucleus. These findings contribute to a better understanding of the neuromuscular control of airway collapse during sleep and the potential development of new drugs for improving upper airway tone in individuals with sleep apnea.