Central Orexin‐A Activates Hypothalamic‐Pituitary‐Adrenal Axis and Stimulates Hypothalamic Corticotropin Releasing Factor and Arginine Vasopressin Neurones in Conscious Rats

Al-Barazanji, K. A.; Wilson, Shelagh; Baker, Jennifer R.; Jessop, David S.; Harbuz, Michael S.

doi:10.1046/j.1365-2826.2001.00655.x

Cited by 128 publications

(79 citation statements)

References 24 publications

(42 reference statements)

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“…Administration of hcrt-1 activates the HPA axis (Hagan et al, 1999;Jászberényi et al, 2000;Kuru et al, 2000;Al-Barazanji et al, 2001;Russell et al, 2001), and, conversely, stress increases preprohcrt mRNA contents in mice (Reyes et al, 2003) and activates hypocretin neurons in both rats and mice (Estabrooke et al, 2001;Espana et al, 2003;Winsky-Sommerer et al, 2004). In agreement with these data, we found here that RS activated hypocretinergic neurotransmission in both wild-type and 5-HTT mice (as indicated by c-Fos labeling and hcrt-R1 mRNA expression).…”

Section: Hypocretin Controls Sleep Homeostasis In 5-htt-deficient Micesupporting

confidence: 90%

Altered Sleep Homeostasis after Restraint Stress in5-HTTKnock-Out Male Mice: A Role for Hypocretins

Rachalski¹,

Alexandre²,

Bernard³

et al. 2009

J. Neurosci.

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Section: Hypocretin Controls Sleep Homeostasis In 5-htt-deficient Micesupporting

confidence: 90%

Altered Sleep Homeostasis after Restraint Stress in5-HTTKnock-Out Male Mice: A Role for Hypocretins

Rachalski¹,

Alexandre²,

Bernard³

et al. 2009

J. Neurosci.

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“…Administration of orexins into the cerebral ventricles quickly increased plasma ACTH and subsequently corticosterone levels in a dose-response fashion (13,23). Such effects were explained by the activation of the PVN, as demonstrated by increased c-fos (23) and CRH mRNA levels (1). Intriguingly, the effect of orexins on the hypothalamus-pituitary-adrenal axis is independent of its effects on NPY neurons (34).…”

Section: Discussionmentioning

confidence: 97%

Orexin activation precedes increased NPY expression, hyperphagia, and metabolic changes in response to sleep deprivation

Martins¹,

Marques²,

Tufik³

et al. 2010

American Journal of Physiology-Endocrinology and Metabolism

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Martins PJ, Marques MS, Tufik S, D'Almeida V. Orexin activation precedes increased NPY expression, hyperphagia, and metabolic changes in response to sleep deprivation. Am J Physiol Endocrinol Metab 298: E726 -E734, 2010. First published January 5, 2010 doi:10.1152/ajpendo.00660.2009.-Several pieces of evidence support that sleep duration plays a role in body weight control. Nevertheless, it has been assumed that, after the identification of orexins (hypocretins), the molecular basis of the interaction between sleep and energy homeostasis has been provided. However, no study has verified the relationship between neuropeptide Y (NPY) and orexin changes during hyperphagia induced by sleep deprivation. In the current study we aimed to establish the time course of changes in metabolite, endocrine, and hypothalamic neuropeptide expression of Wistar rats sleep deprived by the platform method for a distinct period (from 24 to 96 h) or sleep restricted for 21 days (SR-21d). Despite changes in the stress hormones, we found no changes in food intake and body weight in the SR-21d group. However, sleep-deprived rats had a 25-35% increase in their food intake from 72 h accompanied by slight weight loss. Such changes were associated with increased hypothalamus mRNA levels of prepro-orexin (PPO) at 24 h followed by NPY at 48 h of sleep deprivation. Conversely, sleep recovery reduced the expression of both PPO and NPY, which rapidly brought the animals to a hypophagic condition. Our data also support that sleep deprivation rapidly increases energy expenditure and therefore leads to a negative energy balance and a reduction in liver glycogen and serum triacylglycerol levels despite the hyperphagia. Interestingly, such changes were associated with increased serum levels of glucagon, corticosterone, and norepinephrine, but no effects on leptin, insulin, or ghrelin were observed. In conclusion, orexin activation accounts for the myriad changes induced by sleep deprivation, especially the hyperphagia induced under stress and a negative energy balance. neuropeptide Y; leptin; glucagon; insulin; liver glycogen; triacylglycerol SEVERAL PIECES OF EVIDENCE support that sleep duration plays a role in body weight control (4, 15, 56). Everson et al. (10), Kushida et al. (24), and Rechtschaffen et al. (46), using an animal model, characterized a syndrome induced in response to sleep deprivation especially composed of a progressive increase in food intake. Interestingly, Spiegel et al. (55) has shown that humans who are sleep restricted for 2 days (sleeping 4 h/night) were hungrier and developed a craving for food with a high carbohydrate content. Later, the hyperphagic behavior during sleep deprivation was attributed to an increase and decrease in the hypothalamic expression of neuropeptide Y (NPY) and proopiomelanocortin (POMC), respectively (20). Supporting such changes in these neuropeptides, earlier studies in different species have found a reduction in circulating levels of leptin in response to sleep loss (11,22,55,56). Although the d...

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“…Pharmacological administration of synthetic orexin in rats resulted in increased release of ACTH and PRL (1,5,13,14,27,28,32), and it is clear that the ability of orexin to stimulate the HPA axis is due primarily to an action in the brain that causes release of corticotrophin-releasing factor (CRF) into the median eminence (and subsequent diffusion into the hypophyseal portal vessels for access to the corticotrophs of the anterior pituitary gland) from parvocellular neurons located in the PVN (1, 13, 14, 27, 28, 32). If this pharmacological action of exogenously administered orexin has physiological relevance, then antagonism of the actions of the endogenous peptide should alter the HPA axis response to physiological stressors.…”

Section: Discussionmentioning

confidence: 99%

Hypocretin/orexin type 1 receptor in brain: role in cardiovascular control and the neuroendocrine response to immobilization stress

Samson

Bagley²,

Ferguson³

et al. 2007

American Journal of Physiology-Regulatory, Integrative and Comp

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Samson WK, Bagley SL, Ferguson AV, White MM. Hypocretin/ orexin type 1 receptor in brain: role in cardiovascular control and the neuroendocrine response to immobilization stress. Am J Physiol Regul Integr Comp Physiol 292: R382-R387, 2007. First published August 10, 2006; doi:10.1152/ajpregu.00496.2006.-Hypocretin/orexin acts pharmacologically in the hypothalamus to stimulate stress hormone secretion at least in part by an action in the hypothalamic paraventricular nucleus, where the peptide's receptors have been localized. In addition, orexin acts in the brain to increase sympathetic tone and, therefore, mean arterial pressure and heart rate. We provide evidence for the role of endogenously produced hypocretin/orexin in the physiological response to immobilization stress and identify the receptor subtype responsible for this action of the peptide. Antagonism of the orexin type 1 receptor (OX 1R) in the brain prevented the ACTHstimulating effect of centrally administered hypocretin/orexin. Furthermore, pretreatment of animals with the OX 1R antagonist blocked the ACTH response to immobilization/restraint stress. The OX 1R antagonist did not, however, block the pharmacological or physiological release of prolactin in these two models. Antagonism of the OX 1R also blocked the central action of orexin to elevate mean arterial pressures and heart rates in conscious rats. These data suggest receptor subtype-selective responses to hypocretin/orexin and provide further evidence for the importance of endogenously produced peptide in the physiological control of stress hormone secretion. autonomic function; hypothalamus; adrenocorticotropin; prolactin IN ADDITION TO THE WELL-CHRONICLED pharmacological actions of the hypocretins/orexins on arousal state (6,23,29,36), the peptides (referred to here simply as orexins) exert a variety of behavioral (24), autonomic (7,15,34), and endocrine (1, 5, 7, 13, 22, 26 -28, 31, 32) actions mediated by the two characterized binding proteins, the orexin type 1 (OX 1 R) and the orexin type 2 (OX 2 R) receptors (29). Although orexin A and orexin B have many common pharmacological effects, some actions unique to one and not the other have been reported (7,36). Since orexin A binds with higher affinity to the OX 1 R than orexin B and both isoforms bind with apparently equal affinity to the OX 2 R, many investigators have narrowed their attention to the pharmacological effects of orexin A. Our original studies focused on endocrine, cardiovascular, and behavioral actions of orexin A in the hypothalamus and brain stem (7,32,37,38). We demonstrated direct neuronal actions of orexin in the hypothalamic paraventricular nucleus (PVN) and established that the action of exogenous orexin to stimulate the hypothalamic-pituitary-adrenal (HPA) axis was mediated at least in part by the release of corticotrophin-releasing hormone (CRH) (32). We have attempted to identify the receptor subtype responsible for the cardiovascular and neuroendocrine actions of these peptides and provide evidence for the i...

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Central Orexin‐A Activates Hypothalamic‐Pituitary‐Adrenal Axis and Stimulates Hypothalamic Corticotropin Releasing Factor and Arginine Vasopressin Neurones in Conscious Rats

Cited by 128 publications

References 24 publications

Altered Sleep Homeostasis after Restraint Stress in5-HTTKnock-Out Male Mice: A Role for Hypocretins

Altered Sleep Homeostasis after Restraint Stress in5-HTTKnock-Out Male Mice: A Role for Hypocretins

Orexin activation precedes increased NPY expression, hyperphagia, and metabolic changes in response to sleep deprivation

Hypocretin/orexin type 1 receptor in brain: role in cardiovascular control and the neuroendocrine response to immobilization stress

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