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

Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104-6046, USA.
Neuroscience Letters (Impact Factor: 2.03). 11/2011; 505(2):176-9. DOI: 10.1016/j.neulet.2011.10.015
Source: PubMed


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.

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Available from: Irma Rukhadze,
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    • "This form of respiratory plasticity was referred to as long-term facilitation (Fig. 1). Some of the neuromodulators responsible for initiating long-term facilitation, including serotonin (Fregosi and Mitchell, 1994; Mateika and Narwani, 2009; Millhorn et al., 1980b; Mitchell et al., 2001a,b), norepinephrine (Mody et al., 2011; Stettner et al., 2012) and adenosine (Golder et al., 2008; Hoffman et al., 2010; Hoffman and Mitchell, 2011; Hoffman et al., 2012; Nichols et al., 2012) have been identified. In addition, many components of the cellular pathways involved in the initiation of long-term facilitation have been determined (Dale- Nagle et al., 2010; Hoffman et al., 2012; Macfarlane et al., 2008; Macfarlane and Mitchell, 2009; Macfarlane et al., 2009; Satriotomo et al., 2012). "
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    • "However, we recently found evidence for both structural and functional enhancements of noradrenergic transmission in the brainstem of CIH-exposed rats. Specifically, exposure to CIH resulted in sprouting of noradrenergic terminals in different sensory and motor regions within the lower brainstem (Rukhadze et al., 2010; Mody et al., 2011) and increased endogenous noradrenergic activation of cranial motoneurons (Stettner et al., 2012). Data also suggest that activity of dorsal medullary catecholaminergic neurons is increased 1 day after 7-day exposure to CIH (Knight et al., 2011). "
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