MCH Neurons Regulate Permeability of the Median Eminence Barrier.
Animals
Arcuate Nucleus of Hypothalamus
/ physiology
Blood Vessels
/ physiology
Capillaries
/ physiology
Cell Membrane Permeability
/ physiology
Cell Nucleus
/ physiology
Endothelial Cells
/ physiology
Hypothalamic Hormones
/ physiology
Leptin
/ physiology
Median Eminence
/ blood supply
Melanins
/ physiology
Mice
Neurons
/ physiology
Pituitary Hormones
/ physiology
Primary Cell Culture
Rats
Rats, Sprague-Dawley
Receptors, Vascular Endothelial Growth Factor
/ antagonists & inhibitors
Vascular Endothelial Growth Factor A
/ biosynthesis
MCH neurons
VEGF
blood brain barrier
body weight
energy homeostasis
feeding
fenestrated vessels
hypothalamus
leptin
median eminence
neuroendocrinology
obesity
Journal
Neuron
ISSN: 1097-4199
Titre abrégé: Neuron
Pays: United States
ID NLM: 8809320
Informations de publication
Date de publication:
22 07 2020
22 07 2020
Historique:
received:
03
07
2019
revised:
06
03
2020
accepted:
20
04
2020
pubmed:
15
5
2020
medline:
21
10
2020
entrez:
15
5
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32407670
pii: S0896-6273(20)30312-3
doi: 10.1016/j.neuron.2020.04.020
pmc: PMC7383232
pii:
doi:
Substances chimiques
Hypothalamic Hormones
0
Leptin
0
Melanins
0
Pituitary Hormones
0
Vascular Endothelial Growth Factor A
0
melanin-concentrating hormone
67382-96-1
Receptors, Vascular Endothelial Growth Factor
EC 2.7.10.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
306-319.e9Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests The authors declare no competing interests.
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