title: Orexin (hypocretin) neurons contain dynorphin.
abstract: 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.
authors.affiliation: Department of Neurobiology and Program in Neuroscience, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: T C
authors.initials: TC
authors.lastname: Chou
authors.forename: C E
authors.initials: CE
authors.lastname: Lee
authors.forename: J
authors.initials: J
authors.lastname: Lu
authors.forename: J K
authors.initials: JK
authors.lastname: Elmquist
authors.forename: J
authors.initials: J
authors.lastname: Hara
authors.forename: J T
authors.initials: JT
authors.lastname: Willie
authors.forename: C T
authors.initials: CT
authors.lastname: Beuckmann
authors.forename: R M
authors.initials: RM
authors.lastname: Chemelli
authors.forename: T
authors.initials: T
authors.lastname: Sakurai
authors.forename: M
authors.initials: M
authors.lastname: Yanagisawa
authors.forename: C B
authors.initials: CB
authors.lastname: Saper
authors.forename: T E
authors.initials: TE
authors.lastname: Scammell
mesh_terms: D000818:Animals; D000067699:Ataxin-3; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D004399:Dynorphins / Q000235:genetics / Q000378:metabolism*; D020712:Fornix, Brain / Q000166:cytology / Q000378:metabolism; D007031:Hypothalamus / Q000166:cytology / Q000378:metabolism; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics; D009474:Neurons / Q000378:metabolism*; D009479:Neuropeptides / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins; D000068797:Orexins; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012097:Repressor Proteins; D014157:Transcription Factors
chemical_list: D002352:Carrier Proteins; C000596229:HCRT protein, human; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D009687:Nuclear Proteins; D000068797:Orexins; D011498:Protein Precursors; D012333:RNA, Messenger; D012097:Repressor Proteins; D014157:Transcription Factors; D004399:Dynorphins; C092341:ATXN3 protein, human; D000067699:Ataxin-3; C511594:Atxn3 protein, mouse; C511593:Atxn3 protein, rat