Journal
NEUROSCIENCE
Volume 154, Issue 4, Pages 1639-1647Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuroscience.2008.04.068
Keywords
adrenocorticotropic hormone; metabolic syndrome; norepinephrine; obstructive sleep apnea; paraventricular nucleus; stress
Categories
Funding
- NHLBI NIH HHS [R01 HL086804, R01 HL062579-07, HL062579, R56 HL062579, HL086804, R01 HL062579, P01 HL088052, R01 HL086804-01A1] Funding Source: Medline
- NIMH NIH HHS [R01 MH072672-02, R01 MH072672, MH072672, R56 MH053851, R01 MH053851-11A2, R29 MH053851, MH053851, R01 MH053851] Funding Source: Medline
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Obstructive sleep apnea (OSA) is associated with several pathophysiological conditions, including hypertension, obesity, insulin resistance, hypothalamic-pituitary-adrenal (HPA) dysregulation, and other endocrine and metabolic disturbances comprising the metabolic syndrome. Repeated episodes of hypoxia in OSA may represent a chronic intermittent stress, leading to HPA dysregulation. Alterations in HPA reactivity could then contribute to or exacerbate other pathophysiological processes. We showed previously that another metabolic stressor, chronic intermittent cold stress, enhanced noradrenergic facilitation of acute HPA stress reactivity. In this study, we investigated whether chronic intermittent hypoxia (CIH), a rat model for the arterial hypoxemia that accompanies OSA, similarly sensitizes the HPA response to novel acute stress. Rats were exposed to CIH (alternating cycles of normoxia [3 min at 21% O-2] and hypoxia [3 min at 10% O-2], repeated continuously for 8 h/day during the light portion of the cycle for 7 days). On the day after the final CIH exposure, there were no differences in baseline plasma adrenocorticotropic hormone (ACTH), but the peak ACTH response to 30 min acute immobilization stress was greater in CIH-stressed rats than in controls. Induction of Fos expression by acute immobilization stress was comparable following CIH in several HPA-modulatory brain regions, including the paraventricular nucleus, bed nucleus of the stria terminalis, and amygdala. Fos induction was attenuated in lateral hypothalamus, an HPA-inhibitory region. By contrast, acute Fos induction was enhanced in noradrenergic neurons in the locus coeruleus following CIH exposure. Thus, similar to chronic cold stress, CIH sensitized acute HPA and noradrenergic stress reactivity. Plasticity in the acute stress response is important for long-term adaptation, but may also contribute to pathophysiological conditions associated with states of chronic or repeated stress, such as OSA. Determining the neural mechanisms underlying these adaptations may help us better understand the etiology of such disorders, and inform the development of more effective treatments. (C) 2008 IBRO. Published by Elsevier Ltd. All rights reserved.
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