title: Leptin signaling modulates the activity of urocortin 1 neurons in the mouse nonpreganglionic Edinger-Westphal nucleus.
abstract: A recent study systematically characterized the distribution of the long form of the leptin receptor (LepRb) in the mouse brain and showed substantial LepRb mRNA expression in the nonpreganglionic Edinger-Westphal nucleus (npEW) in the rostroventral part of the midbrain. This nucleus hosts the majority of urocortin 1 (Ucn1) neurons in the rodent brain, and because Ucn1 is a potent satiety hormone and electrical lesioning of the npEW strongly decreases food intake, we have hypothesized a role of npEW-Ucn1 neurons in leptin-controlled food intake. Here, we show by immunohistochemistry that npEW-Ucn1 neurons in the mouse contain LepRb and respond to leptin administration with induction of the Janus kinase 2-signal transducer and activator of transcription 3 pathway, both in vivo and in vitro. Furthermore, systemic leptin administration increases the Ucn1 content of the npEW significantly, whereas in mice that lack LepRb (db/db mice), the npEW contains considerably reduced amount of Ucn1. Finally, we reveal by patch clamping of midbrain Ucn1 neurons that leptin administration reduces the electrical firing activity of the Ucn1 neurons. In conclusion, we provide ample evidence for leptin actions that go beyond leptin's well-known targets in the hypothalamus and propose that leptin can directly influence the activity of the midbrain Ucn1 neurons.
authors.affiliation: Department of Cellular Animal Physiology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen, 6500 GL Nijmegen, The Netherlands.
authors.forename: Lu
authors.initials: L
authors.lastname: Xu
authors.forename: Wim J J M
authors.initials: WJ
authors.lastname: Scheenen
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Leshan
authors.forename: Christa M
authors.initials: CM
authors.lastname: Patterson
authors.forename: Carol F
authors.initials: CF
authors.lastname: Elias
authors.forename: Sanne
authors.initials: S
authors.lastname: Bouwhuis
authors.forename: Eric Willem
authors.initials: EW
authors.lastname: Roubos
authors.forename: Martin G
authors.initials: MG
authors.lastname: Myers
authors.forename: Tamás
authors.initials: T
authors.lastname: Kozicz
mesh_terms: D000818:Animals; D015870:Gene Expression; D020738:Leptin / Q000378:metabolism*; D008297:Male; D008636:Mesencephalon / Q000166:cytology; D051379:Mice; D009474:Neurons / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D054411:Receptors, Leptin / Q000235:genetics / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D054832:Urocortins / Q000235:genetics / Q000378:metabolism*
chemical_list: D020738:Leptin; D054411:Receptors, Leptin; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D054832:Urocortins