Contribution of Neurochemical Inputs to the Decrease of Motoneuron Excitability During Non-REM and REM Sleep: A Systematic Review

The sleep-related depression of excitability of upper airway motoneurons is a major neurological cause of obstructive sleep apnea whereas a disruption in the inhibition of spinal motoneurons during rapid eye movement (REM) sleep causes the REM sleep behavioral disorder. The large amount of experimental data has been obtained that deal with neurochemical mechanisms that are responsible for sleep-related depression of various motoneuron groups. However, there is a disagreement regarding the outcome of these studies primarily due to the use of different animal models and approaches, as well as due to differences in quantification and interpretation of obtained results. In this study, we sought to apply the same calculation methodology in order to uniformly quantify and compare the relative contribution of excitatory or inhibitory inputs to the decrease of excitability of different motoneuronal pools during REM and/or non-REM sleep. We analyzed only published quantitative data that were obtained by using receptor antagonists or chemogenetic approach to block receptors or silence neuronal populations. The outcomes of this analysis highlight the differences in the neurotransmitter mechanisms of sleep-related motoneuron depression between different motoneuronal pools and demonstrate the consistency of these mechanisms for hypoglossal motoneurons among various animal models

Neuroanatomical Basis of State-Dependent Activity of Upper Airway Muscles

Obstructive Sleep Apnea (OSA) is a common sleep-related respiratory disorder that is associated with cognitive, cardiovascular, and metabolic morbidities. The major cause of OSA is the sleep-related reduction of upper airway muscle tone that leads to airway obstructions in individuals with anatomically narrow upper airway. This reduction is mainly due to the suppressant effect of sleep on hypoglossal motoneurons that innervate upper airway muscles. The hypoglossal motoneurons have state-dependent activity, which is decreased during the transition from wakefulness to non-rapid eye movement sleep and is further suppressed during rapid eye movement sleep. Multiple neurotransmitters and their receptors have been implicated in the control of hypoglossal motoneuron activity across the sleep-wake states. However, to date, the results of the rigorous testing show that withdrawal of noradrenergic excitation and cholinergic inhibition essentially contribute to the depression of hypoglossal motoneuron activity during sleep. The present review will focus on origins of noradrenergic and cholinergic innervation of hypoglossal motoneurons and the functional role of these neurons in the state-dependent activity of hypoglossal motoneurons

A review of \u3cem\u3eOrthochirus\u3c/em\u3e from Turkey, Iraq, and Iran (Khoozestan, Ilam, and Lorestan Provinces), with descriptions of three new species (Scorpiones: Buthidae)

Three new species, Orthochirus fomichevi sp. n. from Turkey and Iraq, O. gantenbeini sp. n. from Iran (Khoozestan Province), and O. navidpouri sp. n. from Iran (Khoozestan and Lorestan Provinces) are described, compared with other Orthochirus species from the region, and fully illustrated with color photos. Lectotype of O. mesopotamicus Birula, 1918 stat. n. from Iran (Khoozestan Province) is designated. Emended diagnoses are given for O. iranus Kovařík, 2004, O. iraqus Kovařík, 2004, O. mesopotamicus Birula, 1918 stat. n., and O. zagrosensis Kovařík, 2004. A key and a distribution map are included

Glucoregulatory Consequences and Cardiorespiratory Parameters in Rats Exposed to Chronic–Intermittent Hypoxia: Effects of the Duration of Exposure and Losartan

Background: Obstructive sleep apnea (OSA) is associated with glucose intolerance. Both chronic sleep disruption and recurrent blood oxygen desaturations (chronic–intermittent hypoxia, CIH) may cause, or exacerbate, metabolic derangements. Methods: To assess the impact of CIH alone, without accompanying upper airway obstructions, on the counter-regulatory response to glucose load and cardiorespiratory parameters, we exposed adult male Sprague-Dawley rats to CIH or sham room air exchanges for 10 h/day for 7, 21, or 35 days and then, 1 day after conclusion of CIH exposure, conducted intravenous glucose-tolerance tests (ivgtt) under urethane anesthesia. Additional rats underwent 35 days of CIH followed by 35 days of regular housing, or had 35 day-long CIH exposure combined with daily administration of the type 1 angiotensin II receptor antagonist, losartan (15 mg/kg, p.o.), and then were also subjected to ivgtt. Results: Compared with the corresponding control groups, CIH rats had progressively reduced glucose-stimulated insulin release and impaired glucose clearance, only mildly elevated heart rate and/or arterial blood pressure and slightly reduced respiratory rate. The differences in insulin release between the CIH and sham-treated rats disappeared in the rats normally housed for 35 days after 35 days of CIH/sham exposure. The losartan-treated rats had improved insulin sensitivity, with no evidence of suppressed insulin release in the CIH group. Conclusion: In adult rats, the glucose-stimulated insulin release is gradually suppressed with the duration of exposure to CIH, but the effect is reversible. Elimination of the detrimental effect of CIH on insulin release by losartan suggests that CIH disrupts glucoregulation through angiotensin/catecholaminergic pathways. Accordingly, treatment with continuous positive airway pressure may ameliorate pre-diabetic conditions in OSA patients, in part, by reducing sympathoexcitatory effects of recurrent nocturnal hypoxia

Chronic intermittent hypoxia attenuates noradrenergic innervation of hypoglossal motor nucleus

The state-dependent noradrenergic activation of hypoglossal motoneurons plays an important role in the maintenance of upper airway patency and pathophysiology of obstructive sleep apnea (OSA). Chronic intermittent hypoxia (CIH), a major pathogenic factor of OSA, contributes to the risk for developing neurodegenerative disorders in OSA patients. Using anterograde tracer, channelrhodopsin-2, we mapped axonal projections from noradrenergic A7 and SubCoeruleus neurons to hypoglossal nucleus in DBH-cre mice and assessed the effect of CIH on these projections. We found that CIH significantly reduced the number of axonal projections from SubCoeruleus neurons to both dorsal (by 68%) and to ventral (by73%) subregions of the hypoglossal motor nucleus compared to sham-treated animals. The animals' body weight was also negatively affected by CIH. Both effects, the decrease in axonal projections and body weight, were more pronounced in male than female mice, which was likely caused by less sensitivity of female mice to CIH as compared to males. The A7 neurons appeared to have limited projections to the hypoglossal nucleus. Our findings suggest that CIH-induced reduction of noradrenergic innervation of hypoglossal motoneurons may exacerbate progression of OSA, especially in men