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.
| Original language | English |
|---|---|
| Journal | Neuron |
| Volume | 107 |
| Issue number | 2 |
| Pages (from-to) | 306-319.e9 |
| ISSN | 0896-6273 |
| DOIs | |
| Publication status | Published - 22.07.2020 |
Funding
We are grateful for the help of Sebastian Abele from University of Lübeck and Daniele Mazur from University of Lille during Ca 2+ imaging and electron microscopy experiments, respectively. Also, we are grateful for the participation of Dr. Jorge Boucas and Dr. Franziska Metge from the bioinformatics core facility at the Max Planck Institute for Biology of Ageing during initial steps of single nucleus sequencing data analysis and Dr. Astrid Schauss and Dr. Christian Jüngst from the CECAD imaging facility for imaging support. We thank Philipp Hammerschmidt and Dr. Alexander Jais for input on the manuscript. We thank Dr. Matteo Oliverio for graphical abstract design. The research leading to these results has, in part, received funding from a cooperation agreement with Novo Nordisk, Denmark . J.C.B. received funding by the DFG within the framework of the Excellence Initiative by German Federal and State Governments (CECAD). Moreover, the research leading to these results has received funding from the European Union Seventh Framework Program (FP7/2007-2013) under grant agreement no. 266408 to J.C.B. and the European Research Council Synergy Program under grant agreement no. 810331 to V.P. and M.S.
Research Areas and Centers
- Academic Focus: Center for Brain, Behavior and Metabolism (CBBM)
