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MCH neurons regulate permeability of the median eminence barrier

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Item Type:Article
Title:MCH neurons regulate permeability of the median eminence barrier
Creators Name:Jiang, H. and Gallet, S. and Klemm, P. and Scholl, P. and Folz-Donahue, K. and Altmüller, J. and Alber, J. and Heilinger, C. and Kukat, C. and Loyens, A. and Müller-Fielitz, H. and Sundaram, S. and Schwaninger, M. and Prevot, V. and Brüning, J.C.
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.
Keywords:MCH Neurons, Hypothalamus, Median Eminence, VEGF, Energy Homeostasis, Leptin, Obesity, Blood Brain Barrier, Fenestrated Vessels, Feeding, Body Weight, Neuroendocrinology, Animals, Mice, Rats
Publisher:Cell Press
Page Range:306-319
Date:22 July 2020
Official Publication:https://doi.org/10.1016/j.neuron.2020.04.020
PubMed:View item in PubMed

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