期刊
EXPERIMENTAL NEUROLOGY
卷 223, 期 2, 页码 634-644出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.expneurol.2010.02.013
关键词
Peptide receptors; Sleep apnea; Hypertension; Respiratory reflexes; Substance P
资金
- NIH [HL18974, HL096571]
Chronic intermittent hypoxia (CIH) is a frequent concomitant of sleep apnea, which can increase sympathetic nerve activity through mechanisms involving chemoreceptor inputs to the commissural nucleus of the solitary tract (cNTS). These chemosensory inputs co-store glutamate and substance P (SP), an endogenous ligand for neurokinin-1 (NK1) receptors. Acute hypoxia results in internalization of NK1 receptors, suggesting that OH also may affect the subcellular distribution of NK1 receptors in subpopulations of cNTS neurons, some of which may express tyrosine hydroxylase, the rate-limiting enzyme for catecholamine synthesis (TH). To test this hypothesis, we examined dual immunolabeling for the NK1 receptor and TH in the cNTS of male mice subjected to 10 days or 35 days of CIH or intermittent air. Electron microscopy revealed that NK1 receptors and TH were almost exclusively localized within separate somatodendritic profiles in cNTS of control mice. In dendrites, immunogold particles identifying NK1 receptors were prevalent in the cytoplasm and on the plasmalemmal surface. Compared with controls, CIH produced a significant region-specific decrease in the cytoplasmic (10 and 35 days, P<0.05, unpaired Student t-test) and extrasynaptic plasmalemmal (35 days, P<0.01, unpaired Student t-test) density of NK1 immunogold particles exclusively in small (<0.1 mu m) dendrites without TH immunoreactivity. These results suggest that CIH produces a duration-dependent reduction in the availability of NK1 receptors preferentially in small dendrites of non-catecholaminergic neurons in the cNTS. The implications of our findings are discussed with respect to their potential involvement in the slowly developing hypertension seen in sleep apnea patients. (C) 2010 Elsevier Inc. All rights reserved.
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