Rats subjected to chronic-intermittent hypoxia have increased density of noradrenergic terminals in the trigeminal sensory and motor nuclei.

Rodents subjected to chronic intermittent hypoxia (CIH) are used to investigate the mechanisms underlying the consequences of the obstructive sleep apnea (OSA) syndrome. Following CIH, rats have an increased density of noradrenergic terminals in the hypoglossal motor nucleus which innervates lingual muscles that protect the upper airway from collapse in OSA patients. Here, we investigated whether such an increase also occurs in other brainstem nuclei. Six pairs of male Sprague-Dawley rats were exposed to CIH or sham treatment for 10h/day for 35 days, with O(2) level oscillating between 24% and 7% every 3min. Brainstem sections were immunohistochemically processed for dopamine-β-hydroxylase, a marker for norepinephrine. Noradrenergic terminal varicosities were counted in the center of the trigeminal motor nucleus (Mo5) and the interpolar part of the spinal trigeminal sensory nucleus (Sp5). In the Mo5, noradrenergic varicosities tended to be 9% more numerous in CIH- than sham-treated rats, and in the Sp5 they were 18% more numerous in CIH rats (184±9 vs. 156±8 per 100×100μm counting box; p=0.03, n=18 section pairs).These data suggest that CIH elicits sprouting of noradrenergic terminals in multiple motor and sensory regions of the lower brainstem. This may alter motor and cardiorespiratory outputs and the transmission of cardiorespiratory and motor reflexes in CIH rats and, by implication, in OSA patients.