TY - JOUR
T1 - MCH Neurons Regulate Permeability of the Median Eminence Barrier
AU - Jiang, Hong
AU - Gallet, Sarah
AU - Klemm, Paul
AU - Scholl, Pia
AU - Folz-Donahue, Kat
AU - Altmüller, Janine
AU - Alber, Jens
AU - Heilinger, Christian
AU - Kukat, Christian
AU - Loyens, Anne
AU - Müller-Fielitz, Helge
AU - Sundaram, Sivaraj
AU - Schwaninger, Markus
AU - Prevot, Vincent
AU - Brüning, Jens C.
N1 - Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.
PY - 2020/7/22
Y1 - 2020/7/22
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85085330510&partnerID=8YFLogxK
U2 - 10.1016/j.neuron.2020.04.020
DO - 10.1016/j.neuron.2020.04.020
M3 - Journal articles
C2 - 32407670
AN - SCOPUS:85085330510
SN - 0896-6273
VL - 107
SP - 306-319.e9
JO - Neuron
JF - Neuron
IS - 2
ER -