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MCH Neurons Regulate Permeability of the Median Eminence Barrier.

Authors :: Jiang H
Gallet S
Klemm P
Scholl P
Folz-Donahue K
Altmüller J
Alber J
Heilinger C
Kukat C
Loyens A
Müller-Fielitz H
Sundaram S
Schwaninger M
Prevot V
Brüning JC
Source :: Neuron [Neuron] 2020 Jul 22; Vol. 107 (2), pp. 306-319.e9. Date of Electronic Publication: 2020 May 13.
Publication Year :: 2020
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.<br />Competing Interests: Declaration of Interests The authors declare no competing interests.<br /> (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)