小柯机器人

德国科隆大学Jens C. Brning研究组取得一项最新进展。他们通过交叉靶向揭示下丘脑中功能不同的表达促黑素皮质激素（POMC）的神经元亚群。相关论文于2021年5月17日发表于国际顶尖学术期刊《自然-神经科学》杂志上。

他们已经开发出新的小鼠模型，其中交叉的Cre / Dre依赖型重组成功地表达，并对表达瘦素受体（Lepr）和胰高血糖素样肽1受体（Glp1r）的不同POMC神经元进行标记、翻译谱分析和功能表征。他们的实验表明，POMCLepr +和POMCGlp1r +神经元在很大程度上代表了不重叠的亚群，具有不同的基本电生理特性。它们在弓形核内表现出特定的解剖分布，并能差异表达能量状态交流激素和神经递质的受体。最后，他们确定了这些亚群抑制进食的差异能力。总之，他们揭示了关键的代谢调节神经元的明显不同的功能微体系结构。

据了解，下丘脑弓状核中表达POMC的神经元代表代谢稳态的关键调节器。电生理学和单细胞测序实验表明，这些神经元具有显著程度的异质性。但是，这种异质性的确切分子基础和功能后果尚未得到解决。

附：英文原文

Title: Functionally distinct POMC-expressing neuron subpopulations in hypothalamus revealed by intersectional targeting

Author: Nasim Biglari, Isabella Gaziano, Jonas Schumacher, Jan Radermacher, Lars Paeger, Paul Klemm, Weiyi Chen, Svenja Corneliussen, Claudia M. Wunderlich, Michael Sue, Stefan Vollmar, Tim Klckener, Tamara Sotelo-Hitschfeld, Amin Abbasloo, Frank Edenhofer, Frank Reimann, Fiona M. Gribble, Henning Fenselau, Peter Kloppenburg, Frank T. Wunderlich, Jens C. Brning

Issue&Volume: 2021-05-17

Abstract: Pro-opiomelanocortin (POMC)-expressing neurons in the arcuate nucleus of the hypothalamus represent key regulators of metabolic homeostasis. Electrophysiological and single-cell sequencing experiments have revealed a remarkable degree of heterogeneity of these neurons. However, the exact molecular basis and functional consequences of this heterogeneity have not yet been addressed. Here, we have developed new mouse models in which intersectional Cre/Dre-dependent recombination allowed for successful labeling, translational profiling and functional characterization of distinct POMC neurons expressing the leptin receptor (Lepr) and glucagon like peptide 1 receptor (Glp1r). Our experiments reveal that POMCLepr+ and POMCGlp1r+ neurons represent largely nonoverlapping subpopulations with distinct basic electrophysiological properties. They exhibit a specific anatomical distribution within the arcuate nucleus and differentially express receptors for energy-state communicating hormones and neurotransmitters. Finally, we identify a differential ability of these subpopulations to suppress feeding. Collectively, we reveal a notably distinct functional microarchitecture of critical metabolism-regulatory neurons. Biglari et al. reveal subgroups of arcuate nucleus hypothalamic neurons that exhibit distinct molecular signatures and feeding-regulatory functions, thus uncovering new regulatory principles in body weight control.

DOI: 10.1038/s41593-021-00854-0

Source: https://www.nature.com/articles/s41593-021-00854-0

Nature Neuroscience：《自然—神经科学》，创刊于1998年。隶属于施普林格·自然出版集团，最新IF：28.771
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