Fluctuation of extracellular hypocretin‐1 (orexin A) levels in the rat in relation to the light–dark cycle and sleep–wake activities

Yoshida, Yasushi; Fujiki, Nobuhiro; Nakajima, T.; Ripley, Beth; Matsumura, Hitoshi; Yanagawa, Hiroshi; Mignot, Emmanuel; Nishino, Seiji

doi:10.1046/j.0953-816x.2001.01725.x

Cited by 417 publications

(232 citation statements)

References 39 publications

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“…The arousal mediated by hypocretin neurons may be modulated by the energy state (Yamanaka et al, 2003b). That the two systems may subserve somewhat different functions is supported by analyses of daily rhythms; NE levels are reported to increase at the beginning of the wake period, whereas hypocretin levels increase later in the wake period (Mitome et al, 1994;Mochizuki and Scammell, 2003;Zeitzer et al, 2003), consistent with the view that hypocretin may generally oppose sleepiness during periods of prolonged wakefulness (Yoshida et al, 2001), whereas NE increases rapidly after waking.…”

Section: Functional Importance Of Ne Inhibition Of the Hypocretin Arosupporting

confidence: 64%

Direct and Indirect Inhibition by Catecholamines of Hypocretin/Orexin Neurons

Liu¹,

Pol²

2005

J. Neurosci.

112

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Hypothalamic hypocretin enhances arousal, similar to the actions of norepinephrine (NE). The physiological actions of NE were examined in hypocretin neurons identified by selective green fluorescent protein expression in transgenic mouse hypothalamic slices using whole-cell recording. NE induced an outward current, inhibited spike frequency, and hyperpolarized hypocretin neurons dose dependently. Similar actions were evoked by the selective ␣2 adrenergic agonist clonidine. The ␣2 antagonist idazoxan increased spike frequency, suggesting tonic NE-mediated inhibition. The NE-induced current was inwardly rectified, and the reversal potential was dependent on external potassium concentration; it was blocked by barium in the bath and by GTP-␥-S in the pipette, suggesting activation of a G-protein inward rectifying K ϩ (GIRK) current. NE and clonidine decreased calcium currents evoked by depolarizing voltage steps. The selective ␣1 adrenergic agonist phenylephrine had no effect on membrane potential but did increase IPSC frequency; miniature IPSC frequency was also increased, in some cells without any effect on amplitude, suggesting a facilitative presynaptic action at ␣1 receptors on GABAergic axons that innervate hypocretin neurons. NE therefore inhibits hypocretin neurons directly through two mechanisms: activation of a GIRK current, depression of calcium currents, and indirectly through increased inhibitory GABA input. Similar to NE, dopamine and epinephrine reduced or blocked spikes and, in the presence of TTX, showed direct hyperpolarizing actions. The action of dopamine was blocked by the D2 receptor antagonist eticlopride, whereas a D1/5 antagonist had no effect. These data suggest that catecholamines evoke strong inhibitory actions on hypocretin neurons and suggest negative feedback from catecholamine cells that may be excited by hypocretin.

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Section: Functional Importance Of Ne Inhibition Of the Hypocretin Arosupporting

confidence: 64%

Direct and Indirect Inhibition by Catecholamines of Hypocretin/Orexin Neurons

Liu¹,

Pol²

2005

J. Neurosci.

112

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“…Receptors for orexin-A are located on neurons in many different brain regions making it possible for this peptide, once released, to activate a large number of areas affected by sleep and sleep deprivation (Hagan et al, 1999;Bourgin et al, 2000;Kilduff and Peyron, 2000;Piper et al, 2000;Gerashchenko et al, 2001;Yoshida et al, 2001;Wu et al, 2002;Peever et al, 2003;Lee et al, 2005;Mileykovskiy et al, 2005;Vittoz and Berridge 2006), It has recently been shown that manipulation of this system via administration of a orexin antagonist can increase sleep in rats, dogs and humans (Brisbare-Roch et al, 2007). The loss of orexin cells has been shown to cause human and animal narcolepsy (Chemelli et al, 1999;Lin et al, 1999;Nishino et al, 2000;Peyron et al, 2000;Thannickal et al, 2000;Gerashchenko et al, 2001;Wu et al, 2002;Mieda et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Systemic and Nasal Delivery of Orexin-A (Hypocretin-1) Reduces the Effects of Sleep Deprivation on Cognitive Performance in Nonhuman Primates

Deadwyler¹,

Porrino²,

Siegel³

et al. 2007

J. Neurosci.

242

192

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Hypocretin-1 (orexin-A) was administered to sleep-deprived (30 -36 h) rhesus monkeys immediately preceding testing on a multi-image delayed match-to-sample (DMS) short-term memory task. The DMS task used multiple delays and stimulus images and effectively measures cognitive defects produced by sleep deprivation (Porrino et al., 2005). Two methods of administration of orexin-A were tested, intravenous injections (2.5-10.0 g/kg, i.v.) and a novel method developed for nasal delivery via an atomizer spray mist to the nostrils (dose estimated 1.0 g/kg). Results showed that orexin-A delivered via the intravenous and nasal routes significantly improved performance in sleep-deprived monkeys; however, the nasal delivery method was significantly more effective than the highest dose (10 g/kg) of intravenous orexin-A tested. The improvement in performance by orexin-A was specific to trials classified as high versus low cognitive load as determined by performance difficulty under normal testing conditions. Except for the maximum intravenous dose (10 g/kg), neither delivery method affected task performance in alert non-sleep-deprived animals. The improved performance in sleep-deprived animals was accompanied by orexin-A related alterations in local cerebral glucose metabolism (CMRglc) in specific brain regions shown previously to be engaged by the task and impaired by sleep deprivation (Porrino et al., 2005). Consistent with the differential effects on performance, nasal delivered orexin-A produced a more pronounced reversal of sleep deprivation induced changes in brain metabolic activity (CMRglc) than intravenous orexin-A. These findings provide strong evidence for the effectiveness of intranasal orexin-A in alleviating cognitive deficits produced by loss of sleep.

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“…Fluctuations in the extracellular orexin A levels in the lateral hypothalamic area are related to the light/dark cycle and sleep/wakefulness activities, and their release is increased after 6 h of sleep deprivation [28]. Given that orexin has an important role in the regulation of physiological sleep/wakefulness, our results suggest that the impairment of orexin neuronal activities may contribute to an increased amount of NREM sleep in HFD-induced obese mice.…”

Section: Discussionmentioning

confidence: 61%

Hypothalamic prepro-orexin mRNA level is inversely correlated to the non-rapid eye movement sleep level in high-fat diet-induced obese mice

Tanno

Terao

Okamatsu‐Ogura

et al. 2013

Obesity Research & Clinical Practice

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Orexins are hypothalamic neuropeptides, which play important roles in the regulation and maintenance of sleep/wakefulness states and energy homeostasis. To evaluate whether alterations in orexin system is associated with the sleep/wakefulness abnormalities observed in obesity, we examined the mRNA expression of prepro-orexin, orexin receptor type 1, (orexin 1r), and orexin receptor type 2 (oxexin 2r) in the hypothalamus in mice fed with a normal diet (ND) and high-fat diet (HFD)-induced obese mice. We also compared their relationships with sleep/wakefulness. Twenty-four, 4-week-old, male C57BL/6J mice were divided randomly into 3 groups, which received the following: (1) ND for 17 weeks; (2) HFD for 17 weeks; and (3) ND for 7 weeks and HFD for a further 10 weeks. The body weights of mice fed the HFD for 10-17 weeks were 112-150% of the average body weight of the ND group. The daily amount of non-rapid eye movement (NREM) sleep increased significantly in HFD-fed mice. These changes were accompanied by increases in the number but decreases in the duration of each NREM sleep episode. In addition, brief awakenings (<20 s epoch) during NREM sleep was nearly 2-fold more frequent. The mRNA level of prepro-orexin in the hypothalamus was significantly reduced in HFD-induced obese 3 mice, whereas the levels of orexin 1r and orexin 2r were unaffected. The daily amount of NREM sleep was negatively correlated with the hypothalamic prepro-orexin mRNA level, so these results suggest that the increased NREM sleep levels in HFD-induced obese mice are attributable to impaired orexin activity.

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Fluctuation of extracellular hypocretin‐1 (orexin A) levels in the rat in relation to the light–dark cycle and sleep–wake activities

Cited by 417 publications

References 39 publications

Direct and Indirect Inhibition by Catecholamines of Hypocretin/Orexin Neurons

Direct and Indirect Inhibition by Catecholamines of Hypocretin/Orexin Neurons

Systemic and Nasal Delivery of Orexin-A (Hypocretin-1) Reduces the Effects of Sleep Deprivation on Cognitive Performance in Nonhuman Primates

Hypothalamic prepro-orexin mRNA level is inversely correlated to the non-rapid eye movement sleep level in high-fat diet-induced obese mice

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