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心脏和肠道的机械感觉引发小鼠的低代谢和警觉性。

Mechanosensation of the heart and gut elicits hypometabolism and vigilance in mice.

作者信息

Scott Karen A, Tan Yalun, Johnson Dominique N, Elsaafien Khalid, Baumer-Harrison Caitlin, Méndez-Hernández Rebeca, Kirchner Matthew K, Eikenberry Sophia A, Sa Jessica M, Stern Javier E, de Lartigue Guillaume, de Kloet Annette D, Krause Eric G

机构信息

Neuroscience Institute, College of Arts and Sciences, Georgia State University, Atlanta, GA, USA.

Center for Neuroinflammation and Cardiometabolic Diseases, College of Arts and Sciences, Georgia State University, Atlanta, GA, USA.

出版信息

Nat Metab. 2025 Feb;7(2):263-275. doi: 10.1038/s42255-024-01205-6. Epub 2025 Jan 17.

Abstract

Interoception broadly refers to awareness of one's internal milieu. Although the importance of the body-to-brain communication that underlies interoception is implicit, the vagal afferent signalling and corresponding brain circuits that shape perception of the viscera are not entirely clear. Here, we use mice to parse neural circuits subserving interoception of the heart and gut. We determine that vagal sensory neurons expressing the oxytocin receptor (Oxtr), referred to as NG, send projections to cardiovascular or gastrointestinal tissues and exhibit molecular and structural features indicative of mechanosensation. Chemogenetic excitation of NG decreases food and water consumption, and remarkably, produces a torpor-like phenotype characterized by reductions in cardiac output, body temperature and energy expenditure. Chemogenetic excitation of NG also creates patterns of brain activity associated with augmented hypothalamic-pituitary-adrenal axis activity and behavioural indices of vigilance. Recurrent excitation of NG suppresses food intake and lowers body mass, indicating that mechanosensation of the heart and gut can exert enduring effects on energy balance. These findings suggest that the sensation of vascular stretch and gastrointestinal distention may have profound effects on whole-body metabolism and, possibly, mental health.

摘要

内感受广义上是指对自身内部环境的感知。尽管构成内感受基础的身体与大脑之间交流的重要性不言而喻,但塑造内脏感知的迷走神经传入信号和相应的脑回路并不完全清楚。在这里,我们利用小鼠来解析参与心脏和肠道内感受的神经回路。我们确定,表达催产素受体(Oxtr)的迷走感觉神经元(称为NG)向心血管或胃肠道组织发出投射,并表现出指示机械感觉的分子和结构特征。对NG进行化学遗传学刺激会减少食物和水的消耗,而且,会产生一种类似蛰伏的表型,其特征是心输出量、体温和能量消耗降低。对NG进行化学遗传学刺激还会产生与下丘脑 - 垂体 - 肾上腺轴活动增强和警觉行为指标相关的脑活动模式。对NG的反复刺激会抑制食物摄入并降低体重,这表明心脏和肠道的机械感觉可对能量平衡产生持久影响。这些发现表明,血管扩张和胃肠道扩张的感觉可能对全身代谢以及可能的心理健康产生深远影响。

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