title: Hypocretin/orexin- and melanin-concentrating hormone-expressing cells form distinct populations in the rodent lateral hypothalamus: relationship to the neuropeptide Y and agouti gene-related protein systems.
abstract: Cells in the lateral hypothalamus and in the arcuate nucleus play prominent roles in the central control of food intake; however, a neurochemical link connecting these potential components of a hypothalamic circuitry regulating energy metabolism remains to be established. In the present study, the topographical relationship between cells expressing mRNAs encoding melanin-concentrating hormone and the newly discovered neuropeptide family hypocretins/orexins was studied in the rat and mouse lateral hypothalamus by using double-labeling in situ hybridization. Cells expressing the two mRNAs formed completely distinct populations, with hypocretin/orexin cells located primarily perifornically and in the magnocellular lateral hypothalamic nucleus; melanin-concentrating hormone cells extended in a wider area both laterally and periventricularly and appeared to partly surround the hypocretin/orexin population. In the arcuate nucleus, cells expressing neuropeptide Y and agouti gene-related protein were studied by routine fluorescence and/or confocal microscopy immunohistochemistry. Double staining demonstrated that a large proportion of the neuropeptide Y-positive cell bodies in this nucleus also contained agouti gene-related protein-like immunoreactivity. Moreover, these two peptides also coexisted in nerve terminals surrounding and in close relationship to perikarya and processes of both hypocretin/orexin- and melanin-concentrating hormone-immunoreactive cells in the lateral hypothalamus, whereby the former appeared to receive a more dense innervation. These results thus provide evidence for an arcuate-lateral hypothalamic neuropeptide Y/agouti gene-related protein pathway. Furthermore, the results implicate hypocretin/orexin and melanin-concentrating hormone-expressing cells as downstream targets in neuropeptide Y-induced feeding.
authors.affiliation: Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden. Christian.Broberger@neuro.ki.se
authors.forename: C
authors.initials: C
authors.lastname: Broberger
authors.forename: L
authors.initials: L
authors.lastname: De Lecea
authors.forename: J G
authors.initials: JG
authors.lastname: Sutcliffe
authors.forename: T
authors.initials: T
authors.lastname: Hökfelt
mesh_terms: D054369:Agouti-Related Protein; D000818:Animals; D007026:Hypothalamic Area, Lateral / Q000166:cytology* / Q000378:metabolism; D007028:Hypothalamic Hormones / Q000378:metabolism*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D008543:Melanins / Q000378:metabolism*; D051379:Mice; D009478:Neuropeptide Y / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism*; D010907:Pituitary Hormones / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D054369:Agouti-Related Protein; D007028:Hypothalamic Hormones; D036341:Intercellular Signaling Peptides and Proteins; D008543:Melanins; D009478:Neuropeptide Y; D009479:Neuropeptides; D010907:Pituitary Hormones; D011506:Proteins; C019463:melanin-concentrating hormone