Rat Strain and Housing Conditions Alter Oxidative Stress and Hormone Responses to Chronic Intermittent Hypoxia
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Abstract:
Sleep apnea has been associated with elevated risk for metabolic, cognitive, and cardiovascular disorders. Further, the role of hypothalamic-pituitary-adrenal (HPA) activation in sleep apnea has been controversial in human studies. Chronic intermittent hypoxia (CIH) is a rodent model, which mimics the hypoxemia experienced by patients with sleep apnea. Most studies of CIH in rats have been conducted in the Sprague Dawley rat strain. Previously published literature suggests different strains of rats exhibit various responses to disease models, and these effects can be further modulated by the housing conditions experienced by each strain. This variability in response is similar to what has been observed in clinical populations, especially with respect to the HPA system. To investigate if strain or housing (individual or pair-housed) can affect the results of CIH (AHI 8 or 10) treatment, we exposed individual and pair-housed Sprague Dawley and Long-Evans male rats to 7 days of CIH treatment. This was followed by biochemical analysis of circulating hormones, oxidative stress, and neurodegenerative markers. Both strain and housing conditions altered oxidative stress generation, hyperphosphorylated tau protein (tau tangles), circulating corticosterone and adrenocorticotropic hormone (ACTH), and weight metrics. Specifically, pair-housed Long-Evans rats were the most sensitive to CIH, which showed a significant association between oxidative stress generation and HPA activation under conditions of AHI of 8. These results suggest both strain and housing conditions can affect the outcomes of CIH.Keywords:
Corticosterone
Hypoxia
Intermittent hypoxia
A procedure has been developed for determining the amount of corticosterone in mouse and rat brains. Recovery of corticosterone was shown to be between 80 and 90%. Using this procedure, values for basal levels of brain corticosterone have been obtained. Brain corticosterone levels following ether stress were also determined and were shown to change as rapidly as plasma levels. Corticosterone levels in several brain regions as well as its distribution in subcellular fractions have been determined. Chronic injection of ACTH into BALB/cJ female mice elevated brain corticosterone at a time when the plasma levels were not significantly different from those of the saline-injected controls. It is thought that the direct determination of brain corticosterone offers an approach which is potentially enlightening in the study of the interrelationship between plasma glucocorticoids and ACTH secretion. (Endocrinology90: 1091, 1972)
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Corticosterone increases food intake in adrenalectomized rats and plasma corticosterone is 3-fold elevated in intact rats during an overnight fast, suggesting that the steroid may stimulate food intake in intact rats when food is provided. If so, this would present a challenge to maintenance of energy balance. Both chronic and acute effects of corticosterone were tested on feeding the next day after a 15 hour overnight fast in 5-day adrenalectomized rats. Similarly, RU486 was given acutely to intact rats. As expected, adrenalectomized rats replaced at surgery with corticosterone exhibited corticosterone dose-related increases in food intake and insulin levels during the first 8 hours after the fast. By contrast, treatment during the fast of: 1. intact rats with the glucocorticoid receptor antagonist RU486, 2. adrenalectomized steroid-replaced rats, with injections of corticosterone or 3. adrenalectomized rats with injections of corticosterone without prior steroid replacement, did not significantly affect food intake during the first 3–8 hours after the fast. Food intake did increase during 24 hours when previously untreated adrenalectomized rats were treated with corticosterone during the fast. In response to a stressor, acute corticosterone responses of similar magnitude occurred in intact rats both fed and fasted, but this did not affect their food intake during next 24 hours. We conclude that although chronic corticosterone treatment of adrenalectomized rats increases food intake, there is a prolonged lag between corticosterone treatment and increased food intake. Thus, acute corticosterone responses to stressors do not perturb the regulation of energy balance in intact animals; other mechanisms, such as elevated insulin secretion, intervene to blunt the chronic effects of corticosterone on food intake, and thus energy balance.
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Corticosterone
Maternal deprivation
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Sleep apnea syndrome (SAS) is the most common form of sleep-disordered breathing and is associated with many adverse health consequences, including increased overall mortality risk [...]
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A general review was made of studies involving: (1) the relationship between sleep apnea hypopnea syndrome/sleep apnea style intermittent hypoxia and liver injury and (2) the mechanism that causes the liver injury.The data used in this review were mainly from Medline and PubMed published in English from 1993 to February 2009. The search term was "sleep apnea hypopnea syndrome".(1) Clinical and laboratory evidence that sleep apnea hypopnea syndrome and sleep apnea style intermittent hypoxia leads to liver injury; (2) the mechanism that causes the liver injury.The effect of sleep apnea hypopnea syndrome and sleep apnea style intermittent hypoxia on the liver function is characterized by serum aminotransferase elevation. The liver histological injury includes hepatic steatosis, hepatocyte ballooning, lobular inflammation, lobular necrosis, and liver fibrosis. Sleep apnea hypopnea syndrome and sleep apnea style intermittent hypoxia can cause insulin resistance and oxidative stress.Sleep apnea hypopnea syndrome and sleep apnea style intermittent hypoxia can lead to chronic liver injury, which, in most cases, is shown as nonalcoholic fatty liver disease. Insulin resistance and oxidative stress caused by sleep apnea hypopnea syndrome and sleep apnea style intermittent hypoxia play an important role in the mechanism of chronic liver disease development.
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