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


OBJECTIVE
To determine the impact of CIH on neurochemical markers of NE and 5-HT innervation of the XII nucleus.


METHODS
NE and 5-HT terminal varicosities and α₁-adrenergic and 5-HT₂A 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.


RESULTS
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 α₁-adrenoceptors were also approximately 10% more numerous in CIH rats, whereas 5-HT₂A receptor density tended to be lower in CIH rats.


CONCLUSIONS
CIH-elicited increase of NE and 5-HT terminal density and increased expression of α₁-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.
Rukhadze
Irma
I
Department of Animal Biology, University of Pennsylvania, Philadelphia, 19104-6046, USA. rukhadze@vet.upenn.edu
Fenik
Victor B
VB
Benincasa
Kate E
KE
Price
Andrea
A
Kubin
Leszek
L
D000818:Animals; D002452:Cell Count; D006801:Humans; D000860:Hypoxia / Q000473:pathology*; D008297:Male; D008526:Medulla Oblongata / Q000473:pathology* / Q000503:physiopathology; D009046:Motor Neurons / Q000473:pathology / Q000502:physiology; D009638:Norepinephrine / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044402:Receptor, Serotonin, 5-HT2A / Q000502:physiology; D011941:Receptors, Adrenergic / Q000502:physiology*; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology; D011985:Receptors, Serotonin / Q000502:physiology*; D012701:Serotonin / Q000502:physiology; D020181:Sleep Apnea, Obstructive / Q000473:pathology / Q000503:physiopathology
D044402:Receptor, Serotonin, 5-HT2A; D011941:Receptors, Adrenergic; D018340:Receptors, Adrenergic, alpha-1; D011985:Receptors, Serotonin; D012701:Serotonin; D009638:Norepinephrine