Jiang, Hong, Gallet, Sarah, Klemm, Paul ORCID: 0000-0002-5985-1737, Scholl, Pia, Folz-Donahue, Kat, Altmueller, Janine, Alber, Jens, Heilinger, Christian, Kukat, Christian ORCID: 0000-0003-1508-0229, Loyens, Anne, Mueller-Fielitz, Helge, Sundaram, Sivaraj, Schwaninger, Markus, Prevot, Vincent ORCID: 0000-0001-7185-3615 and Bruening, Jens C. (2020). MCH Neurons Regulate Permeability of the Median Eminence Barrier. Neuron, 107 (2). S. 306 - 329. CAMBRIDGE: CELL PRESS. ISSN 1097-4199

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Abstract

Melanin-concentrating hormone (MCH)-expressing neurons are key regulators of energy and glucose homeostasis. Here, we demonstrate that they provide dense projections to the median eminence (ME) in close proximity to tanycytes and fenestrated vessels. Chemogenetic activation of MCH neurons as well as optogenetic stimulation of their projections in the ME enhance permeability of the ME by increasing fenestrated vascular loops and enhance leptin action in the arcuate nucleus of the hypothalamus (ARC). Unbiased phosphoRiboTrap-based assessment of cell activation upon chemogenetic MCH neuron activation reveals MCH-neuron-dependent regulation of endothelial cells. MCH neurons express the vascular endothelial growth factor A (VEGFA), and blocking VEGF-R signaling attenuates the leptin-sensitizing effect of MCH neuron activation. Our experiments reveal that MCH neurons directly regulate permeability of the ME barrier, linking the activity of energy state and sleep regulatory neurons to the regulation of hormone accessibility to the ARC.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Jiang, HongUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gallet, SarahUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Klemm, PaulUNSPECIFIEDorcid.org/0000-0002-5985-1737UNSPECIFIED
Scholl, PiaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Folz-Donahue, KatUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Altmueller, JanineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Alber, JensUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Heilinger, ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kukat, ChristianUNSPECIFIEDorcid.org/0000-0003-1508-0229UNSPECIFIED
Loyens, AnneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mueller-Fielitz, HelgeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sundaram, SivarajUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schwaninger, MarkusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Prevot, VincentUNSPECIFIEDorcid.org/0000-0001-7185-3615UNSPECIFIED
Bruening, Jens C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-325886
DOI: 10.1016/j.neuron.2020.04.020
Journal or Publication Title: Neuron
Volume: 107
Number: 2
Page Range: S. 306 - 329
Date: 2020
Publisher: CELL PRESS
Place of Publication: CAMBRIDGE
ISSN: 1097-4199
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
MELANIN-CONCENTRATING HORMONE; BLOOD-BRAIN-BARRIER; HYPOTHALAMIC MCH; REM-SLEEP; INSULIN SENSITIVITY; LEPTIN RESISTANCE; TRANSGENIC MICE; AGRP NEURONS; RNA-SEQ; ACTIVATIONMultiple languages
NeurosciencesMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/32588

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