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Hypocretin/Orexin neuropeptides: participation in the control of sleep-wakefulness cycle and energy homeostasis.

Nuñez A, Rodrigo-Angulo ML, Andrés ID, Garzón M - Curr Neuropharmacol (2009)

Bottom Line: These hypothalamic neurons are the origin of an extensive and divergent projection system innervating numerous structures of the central nervous system.In this respect, Hcrt/Orx activate two subtypes of G protein-coupled receptors (Hcrt/Orx1R and Hcrt/Orx2R) that show a partly segregated and prominent distribution in neural structures involved in sleep-wakefulness regulation.Wakefulness-enhancing and/or sleep-suppressing actions of Hcrt/Orx have been reported in specific areas of the brainstem.

View Article: PubMed Central - PubMed

Affiliation: Departamento de Anatomía, Histología y Neurociencia, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain. angel.nunez@uam.es

ABSTRACT
Hypocretins or orexins (Hcrt/Orx) are hypothalamic neuropeptides that are synthesized by neurons located mainly in the perifornical area of the posterolateral hypothalamus. These hypothalamic neurons are the origin of an extensive and divergent projection system innervating numerous structures of the central nervous system. In recent years it has become clear that these neuropeptides are involved in the regulation of many organic functions, such as feeding, thermoregulation and neuroendocrine and cardiovascular control, as well as in the control of the sleep-wakefulness cycle. In this respect, Hcrt/Orx activate two subtypes of G protein-coupled receptors (Hcrt/Orx1R and Hcrt/Orx2R) that show a partly segregated and prominent distribution in neural structures involved in sleep-wakefulness regulation. Wakefulness-enhancing and/or sleep-suppressing actions of Hcrt/Orx have been reported in specific areas of the brainstem. Moreover, presently there are animal models of human narcolepsy consisting in modifications of Hcrt/Orx receptors or absence of these peptides. This strongly suggests that narcolepsy is the direct consequence of a hypofunction of the Hcrt/Orx system, which is most likely due to Hcrt/Orx neurons degeneration.The main focus of this review is to update and illustrate the available data on the actions of Hcrt/Orx neuropeptides with special interest in their participation in the control of the sleep-wakefulness cycle and the regulation of energy homeostasis. Current pharmacological treatment of narcolepsy is also discussed.

No MeSH data available.


Related in: MedlinePlus

Distribution of Hcrt/Orx neurons in the cat hypothalamus. A: Microphotograph of a coronal section of cat hypothalamus showing the distribution of orexinergic neurons as result of the immunoreaction for anti-Orexin A antiserum. No counterstaining. B: High magnification of area squared in A. DHA. dorsal hypothalamic area, LHA: lateral hypothalamic area, PeF: perifornical region, 3V: third ventricle. Calibration bars: A, 500 µm, B, 100 µm.
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Figure 2: Distribution of Hcrt/Orx neurons in the cat hypothalamus. A: Microphotograph of a coronal section of cat hypothalamus showing the distribution of orexinergic neurons as result of the immunoreaction for anti-Orexin A antiserum. No counterstaining. B: High magnification of area squared in A. DHA. dorsal hypothalamic area, LHA: lateral hypothalamic area, PeF: perifornical region, 3V: third ventricle. Calibration bars: A, 500 µm, B, 100 µm.

Mentions: The Hcrt/Orx neurons in the rat are restricted to the tuberal region of the hypothalamus, particularly the perifornical region (PeF) and the lateral hypothalamic area (LHA) [18,75]. In the cat, Hcrt/Orx neurons are also concentrated in the same tuberal region, but extend widely to other hypothalamic areas [89,106] (Fig. 2). Hcrt/Orxergic neurons are variable in size (diameter of cell body of 15–40 μm) and shape (spherical, fusiform, multipolar) [16,17,63], and they have been assumed to number from 1,100 to 3,400 in the whole rat brain [34,69]. The human LHA has been estimated to hold about 50,000-80,000 Hcrt/Orx neurons [59]. Hcrt/ Orx axons are very heterogeneous in morphology; they can be either thick and very varicose or thin and slightly varicose [69]. Although Hcrt/Orx neurons are scarce, they have a profuse projection system to numerous brain regions involved in arousal and cortical activation and in sleep-wakefulness cycle regulation. Among the main structures innervated by Hcrt/Orx neurons are the hypothalamus itself, the locus coeruleus (LC), the dorsal raphe nucleus (DR), and the cerebral cortex [50,53]. Hcrt/Orx neurons also innervate the brainstem reticular formation, including the REM sleep inducing region located in the ventral portion of the oral pontine reticular nucleus (vRPO) [66] (Fig. 3).


Hypocretin/Orexin neuropeptides: participation in the control of sleep-wakefulness cycle and energy homeostasis.

Nuñez A, Rodrigo-Angulo ML, Andrés ID, Garzón M - Curr Neuropharmacol (2009)

Distribution of Hcrt/Orx neurons in the cat hypothalamus. A: Microphotograph of a coronal section of cat hypothalamus showing the distribution of orexinergic neurons as result of the immunoreaction for anti-Orexin A antiserum. No counterstaining. B: High magnification of area squared in A. DHA. dorsal hypothalamic area, LHA: lateral hypothalamic area, PeF: perifornical region, 3V: third ventricle. Calibration bars: A, 500 µm, B, 100 µm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2724663&req=5

Figure 2: Distribution of Hcrt/Orx neurons in the cat hypothalamus. A: Microphotograph of a coronal section of cat hypothalamus showing the distribution of orexinergic neurons as result of the immunoreaction for anti-Orexin A antiserum. No counterstaining. B: High magnification of area squared in A. DHA. dorsal hypothalamic area, LHA: lateral hypothalamic area, PeF: perifornical region, 3V: third ventricle. Calibration bars: A, 500 µm, B, 100 µm.
Mentions: The Hcrt/Orx neurons in the rat are restricted to the tuberal region of the hypothalamus, particularly the perifornical region (PeF) and the lateral hypothalamic area (LHA) [18,75]. In the cat, Hcrt/Orx neurons are also concentrated in the same tuberal region, but extend widely to other hypothalamic areas [89,106] (Fig. 2). Hcrt/Orxergic neurons are variable in size (diameter of cell body of 15–40 μm) and shape (spherical, fusiform, multipolar) [16,17,63], and they have been assumed to number from 1,100 to 3,400 in the whole rat brain [34,69]. The human LHA has been estimated to hold about 50,000-80,000 Hcrt/Orx neurons [59]. Hcrt/ Orx axons are very heterogeneous in morphology; they can be either thick and very varicose or thin and slightly varicose [69]. Although Hcrt/Orx neurons are scarce, they have a profuse projection system to numerous brain regions involved in arousal and cortical activation and in sleep-wakefulness cycle regulation. Among the main structures innervated by Hcrt/Orx neurons are the hypothalamus itself, the locus coeruleus (LC), the dorsal raphe nucleus (DR), and the cerebral cortex [50,53]. Hcrt/Orx neurons also innervate the brainstem reticular formation, including the REM sleep inducing region located in the ventral portion of the oral pontine reticular nucleus (vRPO) [66] (Fig. 3).

Bottom Line: These hypothalamic neurons are the origin of an extensive and divergent projection system innervating numerous structures of the central nervous system.In this respect, Hcrt/Orx activate two subtypes of G protein-coupled receptors (Hcrt/Orx1R and Hcrt/Orx2R) that show a partly segregated and prominent distribution in neural structures involved in sleep-wakefulness regulation.Wakefulness-enhancing and/or sleep-suppressing actions of Hcrt/Orx have been reported in specific areas of the brainstem.

View Article: PubMed Central - PubMed

Affiliation: Departamento de Anatomía, Histología y Neurociencia, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain. angel.nunez@uam.es

ABSTRACT
Hypocretins or orexins (Hcrt/Orx) are hypothalamic neuropeptides that are synthesized by neurons located mainly in the perifornical area of the posterolateral hypothalamus. These hypothalamic neurons are the origin of an extensive and divergent projection system innervating numerous structures of the central nervous system. In recent years it has become clear that these neuropeptides are involved in the regulation of many organic functions, such as feeding, thermoregulation and neuroendocrine and cardiovascular control, as well as in the control of the sleep-wakefulness cycle. In this respect, Hcrt/Orx activate two subtypes of G protein-coupled receptors (Hcrt/Orx1R and Hcrt/Orx2R) that show a partly segregated and prominent distribution in neural structures involved in sleep-wakefulness regulation. Wakefulness-enhancing and/or sleep-suppressing actions of Hcrt/Orx have been reported in specific areas of the brainstem. Moreover, presently there are animal models of human narcolepsy consisting in modifications of Hcrt/Orx receptors or absence of these peptides. This strongly suggests that narcolepsy is the direct consequence of a hypofunction of the Hcrt/Orx system, which is most likely due to Hcrt/Orx neurons degeneration.The main focus of this review is to update and illustrate the available data on the actions of Hcrt/Orx neuropeptides with special interest in their participation in the control of the sleep-wakefulness cycle and the regulation of energy homeostasis. Current pharmacological treatment of narcolepsy is also discussed.

No MeSH data available.


Related in: MedlinePlus