Leptin signaling modulates the activity of urocortin 1 neurons in the mouse nonpreganglionic Edinger-Westphal nucleus

Lu Xu, Wim J.J.M. Scheenen, Rebecca L. Leshan, Christa M. Patterson, Carol F. Elias, Sanne Bouwhuis, Eric Willem Roubos, Martin G. Myers, Tamás Kozicz

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

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-Ucn1neurons in the mouse contain LepR band respond to leptin administration with induction of the Janus kinase 2-signal transducer and activator of transcription 3 pathway, both in vivoandin 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.

Original languageEnglish (US)
Pages (from-to)979-988
Number of pages10
JournalEndocrinology
Volume152
Issue number3
DOIs
StatePublished - Mar 2011

ASJC Scopus subject areas

  • Endocrinology

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