QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chou, T. C. Articles by Scammell, T. E. Search for Related Content PubMed PubMed Citation Articles by Chou, T. C. Articles by Scammell, T. E. Pubmed/NCBI databases Compound via MeSH Substance via MeSH

 Previous Article  |  Next Article 

The Journal of Neuroscience, 2001, 21:RC168:1-6

RAPID COMMUNICATION
Orexin (Hypocretin) Neurons Contain Dynorphin

Thomas C. Chou¹, Charlotte E. Lee², J. Lu³, Joel K. Elmquist², Junko Hara⁵, Jon T. Willie⁴, Carsten T. Beuckmann⁴, Richard M. Chemelli⁴, Takeshi Sakurai⁵, Masashi Yanagisawa⁴, Clifford B. Saper^{1, 3}, and Thomas E. Scammell³

¹ Department of Neurobiology and Program in Neuroscience, Harvard Medical School, Boston, Massachusetts 02115, Departments of ² Endocrinology and ³ Neurology, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02115, ⁴ Howard Hughes Medical Institute and Department of Molecular Genetics, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390, and ⁵ Department of Pharmacology, Institute of Basic Medical Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan

Orexins (also called hypocretins) are peptide neurotransmitters expressed in neurons of the lateral hypothalamic area (LHA). Mice lacking the orexin peptides develop narcolepsy-like symptoms, whereas mice with a selective loss of the orexin neurons develop hypophagia and severe obesity in addition to the narcolepsy phenotype. These different phenotypes suggest that orexin neurons may contain neurotransmitters besides orexin that regulate feeding and energy balance. Dynorphin neurons are common in the LHA, and dynorphin has been shown to influence feeding; hence, we studied whether dynorphin and orexin are colocalized. In rats, double-label in situ hybridization revealed that nearly all (94%) neurons expressing prepro-orexin mRNA also expressed prodynorphin mRNA. The converse was also true: 96% of neurons in the LHA containing prodynorphin mRNA also expressed prepro-orexin mRNA. Double-label immunohistochemistry confirmed that orexin-A and dynorphin-A peptides were highly colocalized in the LHA. Wild-type mice and orexin knock-out mice showed abundant prodynorphin mRNA-expressing neurons in the LHA, but orexin/ataxin-3 mice with a selective loss of the orexin neurons completely lacked prodynorphin mRNA in this area, further confirming that within the LHA, dynorphin expression is restricted to the orexin neurons. These findings suggest that dynorphin-A may play an important role in the function of the orexin neurons.

Key words: orexin; hypocretin; dynorphin; narcolepsy; obesity; feeding

---

Copyright © Society for Neuroscience  0270-6474//$05.00/0

This article has been cited by other articles:

				N. Tsujino and T. Sakurai Orexin/Hypocretin: A Neuropeptide at the Interface of Sleep, Energy Homeostasis, and Reward System Pharmacol. Rev., June 1, 2009; 61(2): 162 - 176. [Abstract] [Full Text] [PDF]

				R. Parmentier, S. Kolbaev, B. P. Klyuch, D. Vandael, J.-S. Lin, O. Selbach, H. L. Haas, and O. A. Sergeeva Excitation of Histaminergic Tuberomamillary Neurons by Thyrotropin-Releasing Hormone J. Neurosci., April 8, 2009; 29(14): 4471 - 4483. [Abstract] [Full Text] [PDF]

				C. G. Diniz Behn, N. Kopell, E. N. Brown, T. Mochizuki, and T. E. Scammell Delayed Orexin Signaling Consolidates Wakefulness and Sleep: Physiology and Modeling J Neurophysiol, June 1, 2008; 99(6): 3090 - 3103. [Abstract] [Full Text] [PDF]

				S. Zhang, J. M. Zeitzer, T. Sakurai, S. Nishino, and E. Mignot Sleep/wake fragmentation disrupts metabolism in a mouse model of narcolepsy J. Physiol., June 1, 2007; 581(2): 649 - 663. [Abstract] [Full Text] [PDF]

				G.-Q. Chang, O. Karatayev, R. Ahsan, V. Gaysinskaya, Z. Marwil, and S. F. Leibowitz Dietary fat stimulates endogenous enkephalin and dynorphin in the paraventricular nucleus: role of circulating triglycerides Am J Physiol Endocrinol Metab, February 1, 2007; 292(2): E561 - E570. [Abstract] [Full Text] [PDF]

				W. Zhang, T. Sakurai, Y. Fukuda, and T. Kuwaki Orexin neuron-mediated skeletal muscle vasodilation and shift of baroreflex during defense response in mice Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2006; 290(6): R1654 - R1663. [Abstract] [Full Text] [PDF]

				A. Crocker, R. A. Espana, M. Papadopoulou, C. B. Saper, J. Faraco, T. Sakurai, M. Honda, E. Mignot, and T. E. Scammell Concomitant loss of dynorphin, NARP, and orexin in narcolepsy Neurology, October 25, 2005; 65(8): 1184 - 1188. [Abstract] [Full Text] [PDF]

				A. M. Blouin, T. C. Thannickal, P. F. Worley, J. M. Baraban, I. M. Reti, and J. M. Siegel Narp immunostaining of human hypocretin (orexin) neurons: Loss in narcolepsy Neurology, October 25, 2005; 65(8): 1189 - 1192. [Abstract] [Full Text] [PDF]

				E. B. Margolis, G. O. Hjelmstad, A. Bonci, and H. L. Fields Both Kappa and Mu Opioid Agonists Inhibit Glutamatergic Input to Ventral Tegmental Area Neurons J Neurophysiol, June 1, 2005; 93(6): 3086 - 3093. [Abstract] [Full Text] [PDF]

				C. T. Beuckmann, C. M. Sinton, S. C. Williams, J. A. Richardson, R. E. Hammer, T. Sakurai, and M. Yanagisawa Expression of a Poly-Glutamine-Ataxin-3 Transgene in Orexin Neurons Induces Narcolepsy-Cataplexy in the Rat J. Neurosci., May 5, 2004; 24(18): 4469 - 4477. [Abstract] [Full Text] [PDF]

				A. Wichniak, H. Brunner, E. Friess, and T. Pollmacher Successful suppression of cataplectic attacks with tramadol Neurology, September 23, 2003; 61(6): 864 - 865. [Full Text] [PDF]

				A. J. Thorpe, M. A. Mullett, C. Wang, and C. M. Kotz Peptides that Regulate Food Intake: Regional, metabolic, and circadian specificity of lateral hypothalamic orexin A feeding stimulation Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2003; 284(6): R1409 - R1417. [Abstract] [Full Text] [PDF]

				H. Zheng, M. Corkern, I. Stoyanova, L. M. Patterson, R. Tian, and H.-R. Berthoud Peptides that Regulate Food Intake: Appetite-inducing accumbens manipulation activates hypothalamic orexin neurons and inhibits POMC neurons Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2003; 284(6): R1436 - R1444. [Abstract] [Full Text] [PDF]

				D. Georgescu, V. Zachariou, M. Barrot, M. Mieda, J. T. Willie, A. J. Eisch, M. Yanagisawa, E. J. Nestler, and R. J. DiLeone Involvement of the Lateral Hypothalamic Peptide Orexin in Morphine Dependence and Withdrawal J. Neurosci., April 15, 2003; 23(8): 3106 - 3111. [Abstract] [Full Text] [PDF]

				R. Ouedraogo, E. Naslund, and A. L. Kirchgessner Glucose Regulates the Release of Orexin-A From the Endocrine Pancreas Diabetes, January 1, 2003; 52(1): 111 - 117. [Abstract] [Full Text] [PDF]

				J. P. Kukkonen, T. Holmqvist, S. Ammoun, and K. E. O. Akerman Functions of the orexinergic/hypocretinergic system Am J Physiol Cell Physiol, December 1, 2002; 283(6): C1567 - C1591. [Abstract] [Full Text] [PDF]

				J. Fadel, M. Bubser, and A. Y. Deutch Differential Activation of Orexin Neurons by Antipsychotic Drugs Associated with Weight Gain J. Neurosci., August 1, 2002; 22(15): 6742 - 6746. [Abstract] [Full Text] [PDF]

				C. Wang and C. M. Kotz Urocortin in the lateral septal area modulates feeding induced by orexin A in the lateral hypothalamus Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2002; 283(2): R358 - R367. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help