Dataset Information

Chronic intermittent hypoxia alters density of aminergic terminals and receptors in the hypoglossal motor nucleus.

ABSTRACT: Patients with obstructive sleep apnea (OSA) adapt to the anatomical vulnerability of their upper airway by generating increased activity in upper airway-dilating muscles during wakefulness. Norepinephrine (NE) and serotonin (5-HT) mediate, through ??-adrenergic and 5-HT?A receptors, a wake-related excitatory drive to upper airway motoneurons. In patients with OSA, this drive is necessary to maintain their upper airway open. We tested whether chronic intermittent hypoxia (CIH), a major pathogenic factor of OSA, affects aminergic innervation of XII motoneurons that innervate tongue-protruding muscles in a manner that could alter their airway-dilatory action.To determine the impact of CIH on neurochemical markers of NE and 5-HT innervation of the XII nucleus.NE and 5-HT terminal varicosities and ??-adrenergic and 5-HT?A receptors were immunohistochemically visualized and quantified in the XII nucleus in adult rats exposed to CIH or room air exchanges for 10 h/d for 34 to 40 days.CIH-exposed rats had approximately 40% higher density of NE terminals and approximately 20% higher density of 5-HT terminals in the ventromedial quadrant of the XII nucleus, the region that controls tongue protruder muscles, than sham-treated rats. XII motoneurons expressing ??-adrenoceptors were also approximately 10% more numerous in CIH rats, whereas 5-HT?A receptor density tended to be lower in CIH rats.CIH-elicited increase of NE and 5-HT terminal density and increased expression of ??-adrenoceptors in the XII nucleus may lead to augmentation of endogenous aminergic excitatory drives to XII motoneurons, thereby contributing to the increased upper airway motor tone in patients with OSA.

SUBMITTER: Rukhadze I

PROVIDER: S-EPMC3001268 | biostudies-other | 2010 Nov

REPOSITORIES: biostudies-other

ACCESS DATA

Publications

Chronic intermittent hypoxia alters density of aminergic terminals and receptors in the hypoglossal motor nucleus.

Rukhadze Irma I Fenik Victor B VB Benincasa Kate E KE Price Andrea A Kubin Leszek L

American journal of respiratory and critical care medicine 20100709 10

<h4>Rationale</h4>Patients with obstructive sleep apnea (OSA) adapt to the anatomical vulnerability of their upper airway by generating increased activity in upper airway-dilating muscles during wakefulness. Norepinephrine (NE) and serotonin (5-HT) mediate, through α₁-adrenergic and 5-HT₂A receptors, a wake-related excitatory drive to upper airway motoneurons. In patients with OSA, this drive is necessary to maintain their upper airway open. We tested whether chronic intermittent hypoxia (CIH), ...[more]

PMID: 20622040

Similar Datasets

Project description:NEW FINDINGS:What is the central question of this study? Periodic decreases in arterial blood O2 or chronic intermittent hypoxia (CIH) is a hallmark feature of sleep apnoea patients. Despite a large body of clinical evidence linking sleep disordered breathing with apnoeas to diabetes, the causal relationships between CIH and ?-cell function and the underlying molecular mechanisms have not been established. What is the main finding and its importance? In a rodent model, we show that mitochondrial oxidative stress generated by CIH leads to pancreatic ?-cell dysfunction manifested by augmented basal insulin secretion, insulin resistance, defective proinsulin processing and impaired glucose-stimulated insulin secretion. The results of the present study provide evidence for direct effects of CIH on ?-cell function, which may be an underlying molecular mechanism contributing to the development of type 2 diabetes among sleep apnoea patients. Breathing disorders with recurrent apnoea produce periodic decreases in arterial blood O2, i.e. chronic intermittent hypoxia (CIH). Recurrent apnoea patients and CIH-exposed rodents exhibit several co-morbidities, including diabetes. However, the effects of CIH on pancreatic ?-cell function are not known. In the present study, we investigated pancreatic ?-cell function in C57BL6 mice exposed to 30 days of CIH. Compared with control animals, the CIH-exposed mice exhibited elevated levels of fasting plasma insulin but comparable glucose levels and higher homeostasis model assessment, indicating insulin resistance. Pancreatic ?-cell morphology was unaltered in CIH-exposed mice. Insulin content was decreased in CIH-exposed ?-cells, and this effect was associated with increased proinsulin levels. The mRNA and protein levels of the enzyme prohormone convertase 1, which converts proinsulin to insulin, were downregulated in CIH-treated islets. More importantly, glucose-stimulated insulin secretion was impaired in CIH-exposed mice and in isolated islets. Mitochondrial levels of reactive oxygen species (ROS) were elevated in CIH-exposed pancreatic islets. Treatment of mice with mito-tempol, a scavenger of mitochondrial ROS, during exposure to CIH prevented the augmented insulin secretion and restored the proinsulin and homeostasis model assessment values to control levels. These results demonstrate that CIH leads to pancreatic ?-cell dysfunction, manifested by augmented basal insulin secretion, insulin resistance, defective proinsulin processing, impaired glucose-stimulated insulin secretion and increased mitochondrial ROS, which mediate the effects of CIH on pancreatic ?-cell function.

Dataset Information

Chronic intermittent hypoxia alters density of aminergic terminals and receptors in the hypoglossal motor nucleus.

Publications

Chronic intermittent hypoxia alters density of aminergic terminals and receptors in the hypoglossal motor nucleus.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets