Revisiting the Role of Serotonin in Sleep-Disordered Breathing

Abstract

Serotonin or 5-hydroxytryptamine (5-HT) is a ubiquitous neuro-modulator–transmitter that acts in the central nervous system, playing a major role in the control of breathing and other physiological functions. The midbrain, pons, and medulla regions contain several serotonergic nuclei with distinct physiological roles, including regulating the hypercapnic ventilatory response, upper airway patency, and sleep–wake states. Obesity is a major risk factor in the development of sleep-disordered breathing (SDB), such as obstructive sleep apnea (OSA), recurrent closure of the upper airway during sleep, and obesity hypoventilation syndrome (OHS), a condition characterized by daytime hypercapnia and hypoventilation during sleep. Approximately 936 million adults have OSA, and 32 million have OHS worldwide. 5-HT acts on 5-HT receptor subtypes that modulate neural control of breathing and upper airway patency. This article reviews the role of 5-HT in SDB and the current advances in 5-HT-targeted treatments for SDB.

Impact of Serotonergic 5HT1A and 5HT2A Receptor Activation on the Respiratory Response to Hypercapnia in a Rat Model of Parkinson’s Disease

“…Dopaminergic cells in the ventral tegmental area and substantia nigra, and their terminal fields in the paraventricular nucleus, prefrontal cortex and striatum, receive connections from serotonergic raphe nuclei (dorsal and median) [47]. It is also plausible that the reduced concentration of 5-HT in the brainstem present in our study may be due to the degeneration in serotonergic neurons of the raphe nuclei, which are considered to be involved in the hypercapnic ventilatory response (Aung et al, 2024) [23]. Additionally, the RTN, which is crucial in detecting CO2, degenerating in the 6-OHDA model with striatal injection [19], exhibits dense 5-HT innervation, which may provide 5-HT-dependent control of the RTN [4].…”

“…In the central nervous system, serotonin is a neurotransmitter important for many physiological functions, including being involved in the control of breathing, upper airway function, and the pathogenesis of obstructive sleep apnea [5,23]. Ample evidence supports the role of 5-HT neurons that function as central CO 2 chemosensors [24,25], while not much is known about the involvement of the 5-HT 1A and 5-HT 2A receptors in the generation or modulation of the hypercapnic ventilatory response.…”