Hypocretin (orexin) deficiency in human narcolepsy

Nishino, Seiji; Ripley, Beth; Overeem, Sebastiaan; Lammers, Gert Jan; Mignot, Emmanuel

doi:10.1016/s0140-6736(99)05582-8

Cited by 1,615 publications

(797 citation statements)

References 5 publications

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“…These include feeding behavior (1, 3, 4), behavioral activity (5), sleep/awake (6,7,8), energy balance (9) and neuroendocrinological response (10). In addition to these functions, we have shown that intracisternal but not intraperitoneal injection of orexin-A dosedespondently stimulated gastric acid secretion in conscious rats (11).…”

Section: Introductionmentioning

confidence: 95%

Requirement of Intact Disulfide Bonds in Orexin-A-Induced Stimulation of Gastric Acid Secretion That Is Mediated by OX1 Receptor Activation

Okumura

Takeuchi

Motomura

et al. 2001

Biochemical and Biophysical Research Communications

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Orexin-A is a neuropeptide consisting 33 amino acids with two intrachain disulfide bonds, namely Cys6-Cys12 and Cys7-Cys14, and is a potent stimulator of food consumption and gastric acid secretion. In contrast, orexin-B, a peptide containing 28 amino acids without disulfide bond, which has no stimulatory action of gastric acid. The objective of the present study was to characterize the receptor-mediated mechanism of orexin-A-induced stimulation of gastric acid secretion using orexin-A-

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Section: Introductionmentioning

confidence: 95%

Requirement of Intact Disulfide Bonds in Orexin-A-Induced Stimulation of Gastric Acid Secretion That Is Mediated by OX1 Receptor Activation

Okumura

Takeuchi

Motomura

et al. 2001

Biochemical and Biophysical Research Communications

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“…130,131 Like MCH, ORX exerts a stimulatory effect on food intake, although the effect on consolidating sleep/wake states is more profound and clearly established. 121,[128][129][130][131][132] Therefore, it is conceivable that ORX may maintain arousal and locomotor activity, both of which are essential for food-seeking behavior following periods of fasting. 133 Finally, as noted, the distribution of MCH-and ORXpositive terminals is widespread not only in subcortical regions but also in cortical regions.…”

mentioning

confidence: 99%

Body weight is regulated by the brain: a link between feeding and emotion

2005

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Regulated energy homeostasis is fundamental for maintaining life. Unfortunately, this critical process is affected in a high number of mentally ill patients. Eating disorders such as anorexia nervosa are prevalent in modern societies. Impaired appetite and weight loss are common in patients with depression. In addition, the use of neuroleptics frequently produces obesity and diabetes mellitus. However, the neural mechanisms underlying the pathophysiology of these behavioral and metabolic conditions are largely unknown. In this review, we first concentrate on the established brain machinery of food intake and body weight, especially on the melanocortin and neuropeptide Y (NPY) systems as illustration. These systems play a critical role in receiving and processing critical peripheral metabolic cues such as leptin and ghrelin. It is also notable that both systems modulate emotion and motivated behavior as well. Secondly, we discuss the significance and potential promise of multidisciplinary molecular and neuroanatomic techniques that will likely increase the understanding of brain circuitries coordinating energy homeostasis and emotion. Finally, we introduce several lines of evidence suggesting a link between the melanocortin/NPY systems and several neurotransmitter systems on which many of the psychotropic agents exert their influence. Maintaining energy homeostasis is fundamental for survival. However, obesity due to over-nutrition is an increasing worldwide public health problem. 1 In psychiatric practice, on the other hand, impaired appetite is one of the crucial issues. Anorexia and weight loss are common, for example, in patients suffering from depression. Eating disorders are medically intractable and life threatening. In addition, the so-called 'atypical' antipsychotic agents, currently and widely used to treat psychoses, often induce hyperphagia, obesity, and diabetes mellitus. [2][3][4] In the past decade, fortunately, there has been remarkable progress in understanding the molecular mechanisms of food intake and body weight. This is due in large part to increased research activity towards combating the rising incidences of obesity and associated metabolic disorders. As a result, it is now established that the central nervous system (CNS) senses and processes peripheral metabolic cues including leptin 5 and ghrelin, 6,7 resulting in coordinated energy homeostasis. However, the pathophysiology of the disequilibrium between energy intake and expenditure in psychiatric disorders remains largely unknown. Nevertheless, evidence suggests that several CNS systems regulating energy balance may be dysregulated in patients with mental illnesses, for example, eating disorders, and drug addiction. [8][9][10][11][12][13][14] In the current review, we will illustrate the neuroanatomic and molecular genetic aspects of the melanocortin and neuropeptide Y (NPY) systems residing in the CNS downstream of leptin and ghrelin, to discuss the neural bases of feeding, metabolism, and emotion. Additionally, we point the reader to...

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“…First, nine human narcolepsy 6 patients were shown to have very low levels of orexin A in their cerebrospinal fluid (CSF) as compared with healthy controls (11). Postmortem brain studies of human narcolepsy patients subsequently showed no detectable levels of orexin peptides in the cortex and pons, in which orexinergic projections are normally found ( Figure 1A), and an 80-100% reduction in the number of neurons containing detectable prepro-orexin mRNA or orexin-like immunoreactivity in the hypothalamus (12,13).…”

Section: Human Narcolepsy and Orexin Deficiencymentioning

confidence: 99%

Orexin deficiency and narcolepsy

Sakurai¹

2013

Current Opinion in Neurobiology

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Orexin deficiency results in the sleep disorder narcolepsy in many mammalian species, including mice, dogs, and humans, suggesting that the orexin system is particularly important for normal regulation of sleep/wakefulness states, and especially for maintenance of wakefulness. This review discusses animal models of narcolepsy; the contribution of each orexin receptor subtype to the narcoleptic phenotypes; and the etiology of orexin neuronal death. It also raises the possibility of novel therapies targeting the orexin system for sleep disorders including insomia and narcolepsycataplexy.

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Hypocretin (orexin) deficiency in human narcolepsy

Cited by 1,615 publications

References 5 publications

Requirement of Intact Disulfide Bonds in Orexin-A-Induced Stimulation of Gastric Acid Secretion That Is Mediated by OX1 Receptor Activation

Requirement of Intact Disulfide Bonds in Orexin-A-Induced Stimulation of Gastric Acid Secretion That Is Mediated by OX1 Receptor Activation

Body weight is regulated by the brain: a link between feeding and emotion

Orexin deficiency and narcolepsy

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