小柯机器人

2021年11月17日，美国宾夕法尼亚大学J. Nicholas Betley、Scintillon研究所Albert I. Chen等研究人员合作在《自然》杂志发表论文，通过反向转化鉴定到一个小脑的饱腹感网络。

研究人员使用了一种反向转化的方法来鉴定和解剖学上、分子上和功能上描述促进饱腹感的神经组合。无偏见的、基于任务的功能磁共振成像显示，在以贪吃为特征的遗传性疾病患者中，小脑对食物的反应存在明显差异。对小鼠的转录组分析显示，小脑前深部核团（aDCN）中存在分子和区域上的不同神经元，这些神经元会被进食或肠道中的营养物质注入激活。选择性地激活aDCN神经元，通过减少进食量来大幅减少食物摄入，而不对代谢率进行补偿性改变。

研究人员发现，aDCN的活动通过增加纹状体多巴胺水平和减弱对随后食物消耗的阶段性多巴胺反应来终止食物摄入。这项研究定义了一个保守的饱食中心，它可能是管理过度饮食的一个新的治疗靶标，并强调了"从临床到实验室"的方法对于鉴定影响行为的神经回路的效用。

据介绍，大脑是体重平衡之处。然而，人们无法控制日益流行的肥胖症，这突出表明需要超越经典的进食途径，从而扩大人们对体重控制的理解。

附：英文原文

Title: Reverse-translational identification of a cerebellar satiation network

Author: Low, Aloysius Y. T., Goldstein, Nitsan, Gaunt, Jessica R., Huang, Kuei-Pin, Zainolabidin, Norliyana, Yip, Alaric K. K., Carty, Jamie R. E., Choi, Ju Y., Miller, Alekso M., Ho, Helen S. T., Lenherr, Clara, Baltar, Nicholas, Azim, Eiman, Sessions, October M., Chng, Toh Hean, Bruce, Amanda S., Martin, Laura E., Halko, Mark A., Brady, Roscoe O., Holsen, Laura M., Alhadeff, Amber L., Chen, Albert I., Betley, J. Nicholas

Issue&Volume: 2021-11-17

Abstract: The brain is the seat of body weight homeostasis. However, our inability to control the increasing prevalence of obesity highlights a need to look beyond canonical feeding pathways to broaden our understanding of body weight control1,2,3. Here we used a reverse-translational approach to identify and anatomically, molecularly and functionally characterize a neural ensemble that promotes satiation. Unbiased, task-based functional magnetic resonance imaging revealed marked differences in cerebellar responses to food in people with a genetic disorder characterized by insatiable appetite. Transcriptomic analyses in mice revealed molecularly and topographically -distinct neurons in the anterior deep cerebellar nuclei (aDCN) that are activated by feeding or nutrient infusion in the gut. Selective activation of aDCN neurons substantially decreased food intake by reducing meal size without compensatory changes to metabolic rate. We found that aDCN activity terminates food intake by increasing striatal dopamine levels and attenuating the phasic dopamine response to subsequent food consumption. Our study defines a conserved satiation centre that may represent a novel therapeutic target for the management of excessive eating, and underscores the utility of a ‘bedside-to-bench’ approach for the identification of neural circuits that influence behaviour.

DOI: 10.1038/s41586-021-04143-5

Source: https://www.nature.com/articles/s41586-021-04143-5

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