Orexin Directly Excites Orexin Neurons through Orexin 2 Receptor

Yamanaka, Akihiro; Tabuchi, Sawako; Tsunematsu, Tomomi; Fukazawa, Yugo; Tominaga, Makoto

doi:10.1523/jneurosci.2120-10.2010

Cited by 98 publications

(91 citation statements)

References 37 publications

(44 reference statements)

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“…Yoshida et al, 2006). Consistent with these diverse afferents, the OX neurons are found to express different types of receptors, in addition to their own, the OX1R (Backberg, Hervieu, Wilson, & Meister, 2002) and OX2R (Yamanaka, Tabuchi, Tsunematsu, Fukazawa, & Tominaga, 2010). These other receptors include those for serotonin (Collin, Backberg, Onnestam, & Meister, 2002), acetylcholine (Chou, Rotman, & Saper, 2004; Garcia et al, 2015), adenosine (Thakkar, Winston, & McCarley, 2002), GABA (Backberg, Collin, Ovesjo, & Meister, 2003; Backberg, Ultenius, Fritschy, & Meister, 2004), and leptin (Hakansson et al, 1999), although rarely dopamine (Bubser et al, 2005), and also those for the neuropeptides, cholecystokinin (Tsujino et al, 2005), corticotropin-releasing factor (Winsky-Sommerer et al, 2004), neurotensin (Furutani et al, 2013), neuropeptide Y (Fu, Acuna-Goycolea, & van den Pol, 2004), and galanin-like peptide (Kageyama et al, 2006), as well as the mu opioid receptor (Y.…”

Section: Anatomy Of Orexin/hypocretin-expressing Neuronsmentioning

confidence: 94%

Orexin/Hypocretin System: Role in Food and Drug Overconsumption

Barson

Leibowitz

2017

International Review of Neurobiology

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The neuropeptide orexin/hypocretin (OX), while largely transcribed within the hypothalamus, is released throughout the brain to affect complex behaviors. Primarily through the hypothalamus itself, OX homeostatically regulates adaptive behaviors needed for survival, including food intake, sleep-wake regulation, mating, and maternal behavior. However, through extra-hypothalamic limbic brain regions, OX promotes seeking and intake of rewarding substances of abuse, like palatable food, alcohol, nicotine, and cocaine. This neuropeptide, in turn, is stimulated by the intake of or early life exposure to these substances, forming a non-homeostatic, positive feedback loop. The OX receptor involved in these behaviors, adaptive behavior or substance seeking and intake, is dependent on the particular brain region that contributes to them. Thus, we propose that, while the primary function of OX is to maintain arousal for the performance of adaptive behaviors, this neuropeptide system is readily coopted by rewarding substances that involve positive feedback, ultimately promoting their abuse.

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Section: Anatomy Of Orexin/hypocretin-expressing Neuronsmentioning

confidence: 94%

Orexin/Hypocretin System: Role in Food and Drug Overconsumption

Barson

Leibowitz

2017

International Review of Neurobiology

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“…Intracerebroventricular OxA given during ischaemia induced by middle cerebral artery occlusion promoted neuronal survival [108]; this action is mediated via Ox receptor activation and the PI3K/Akt pathway [92,93]. Given that (i) Ox neurons are chemosensitive [104], (ii) they self-stimulate via Ox receptor 2 [106] and (iii) stimulation inhibits activation of caspase 3 [93] this neuroprotective pathway appears likely. In addition, active caspase 3 in Ox neurons is correlated with the presence of coarse granular Ox immunoreactive staining [77].…”

Section: Mechanisms Of Decreased Ox Immunoreactivitymentioning

confidence: 99%

Decreased orexin (hypocretin) immunoreactivity in the hypothalamus and pontine nuclei in sudden infant death syndrome

et al. 2015

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Infants at risk of sudden infant death syndrome (SIDS) have been shown to have dysfunctional sleep and poor arousal thresholds. In animal studies, both these attributes have been linked to impaired signalling of the neuropeptide orexin. This study examined the immunoreactivity of orexin (OxA and OxB) in the tuberal hypothalamus (n = 27) and the pons (n = 15) of infants (1-10 months) who died from SIDS compared to age-matched non-SIDS infants. The percentage of orexin immunoreactive neurons and the total number of neurons were quantified in the dorsomedial, perifornical and lateral hypothalamus at three levels of the tuberal hypothalamus. In the pons, the area of orexin immunoreactive fibres were quantified in the locus coeruleus (LC), dorsal raphe (DR), laterodorsal tegmental (LDT), medial parabrachial, dorsal tegmental (DTg) and pontine nuclei (Pn) using automated methods. OxA and OxB were co-expressed in all hypothalamic and pontine nuclei examined. In SIDS infants, orexin immunoreactivity was decreased by up to 21 % within each of the three levels of the hypothalamus compared to non-SIDS (p ≤ 0.050). In the pons, a 40-50 % decrease in OxA occurred in the all pontine nuclei, while a similar decrease in OxB immunoreactivity was observed in the LC, LDT, DTg and Pn (p ≤ 0.025). No correlations were found between the decreased orexin immunoreactivity and previously identified risk factors for SIDS, including prone sleeping position and cigarette smoke exposure. This finding of reduced orexin immunoreactivity in SIDS infants may be associated with sleep dysfunction and impaired arousal.

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“…A synthetic surrogate ligand for an orphan receptor, BRS-3, also activates these neurons 53 . Recently, orexin itself was shown to activate orexin neurons through OXR-2, suggesting a positive feed back mechanism that maintain orexin neuronal activity 54 .…”

Section: Factors That Regulate Orexin Neuronsmentioning

confidence: 99%

Connectomics of orexin-producing neurons: interface of systems of emotion, energy homeostasis and arousal

Sakurai

Mieda

2011

Trends in Pharmacological Sciences

201

167

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Avoiding danger and finding food, which are life-sustaining activities that are regulated by emotion, reward and energy balance, require proper wakefulness. The orexin system regulates sleep and wakefulness through interactions with systems that regulate emotion, reward and energy homeostasis. This system regulates sleep and wakefulness to occur at appropriate times that are in accordance with our internal and external environments.Recent findings have brought about the possibility of novel therapies targeting orexin 2 system for sleep disorder including insomia and narcolepsy-cataplexy. In this review, we will discuss the current understanding of the integrative physiology and clinical perspectives of the orexin system. The ventrolateral preoptic nucleus (VLPO) is a region of the anterior hypothalamus, which includes sleep-active neurons, which inhibit the major ascending monoaminergic arousal systems during sleep. Lateral hypothalamic area (LHA)The lateral hypothalamus or lateral hypothalamic area is a region of the hypothalamus, generally including the lateral hypothalamic area and lateral preoptic nucleus.Classically, this region is considered as a feeding center. Stimulation of this area causes increased food intake, while bilateral lesion of this area causes cessation of feeding.This region receives input from amygdala. This area contains glucose sensitive neurons, which are inhibited by glucose This region are also critically involved in the regulation of sympathetic nereve function and arousal.

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Orexin Directly Excites Orexin Neurons through Orexin 2 Receptor

Cited by 98 publications

References 37 publications

Orexin/Hypocretin System: Role in Food and Drug Overconsumption

Orexin/Hypocretin System: Role in Food and Drug Overconsumption

Decreased orexin (hypocretin) immunoreactivity in the hypothalamus and pontine nuclei in sudden infant death syndrome

Connectomics of orexin-producing neurons: interface of systems of emotion, energy homeostasis and arousal

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