Max Planck Institute for Metabolism Research, Department of Neuronal Control of Metabolism, Gleueler Str. 50, 50931 Cologne, Germany; Center for Endocrinology, Diabetes and Preventive Medicine (CEDP), University Hospital Cologne, Kerpener Str. 26, 50924 Cologne, Germany; Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (CECAD) and Center of Molecular Medicine Cologne (CMMC), University of Cologne, Joseph-Stelzmann-Str. 26, 50931 Cologne, Germany.
University of Lille, Inserm, CHU Lille, Lille Neuroscience & Cognition Research Center, Development and Plasticity of the Neuroendocrine Brain, UMR-S1172, Lille, France.
Neuron. 2020 Jul 22;107(2):306-319.e9. doi: 10.1016/j.neuron.2020.04.020. Epub 2020 May 13.
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.
黑色素浓缩激素 (MCH) 表达神经元是能量和葡萄糖稳态的关键调节者。在这里，我们证明它们向正中隆起 (ME) 提供密集的投射，与 tanycytes 和有孔血管非常接近。化学遗传激活 MCH 神经元以及光遗传刺激其在 ME 中的投射，通过增加有孔血管环来增强 ME 的通透性，并增强瘦素在下丘脑弓状核 (ARC) 中的作用。化学遗传激活 MCH 神经元后，通过无偏磷酸 RiboTrap 检测细胞激活，揭示了 MCH 神经元对内皮细胞的依赖性调节。MCH 神经元表达血管内皮生长因子 A (VEGFA)，阻断 VEGF-R 信号可减弱 MCH 神经元激活对瘦素增敏的作用。我们的实验表明，MCH 神经元直接调节 ME 屏障的通透性，将能量状态和睡眠调节神经元的活性与激素进入 ARC 的调节联系起来。
