Aldosterone-induced salt appetite requires HSD2 neurons.

IF 6.3 1区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
Silvia Gasparini, Lila Peltekian, Miriam C McDonough, Chidera Ja Mitchell, Marco Hefti, Jon M Resch, Joel C Geerling
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引用次数: 0

Abstract

Excessive aldosterone production increases the risk of heart disease, stroke, dementia, and death. Aldosterone increases both sodium retention and sodium consumption, and increased sodium consumption may worsen end-organ damage in patients with aldosteronism. Preventing this increase could improve outcomes, but the behavioral mechanisms of aldosterone-induced sodium appetite remain unclear. In rodents, we previously identified aldosterone-sensitive neurons, which express the mineralocorticoid receptor and its pre-receptor regulator, 11-beta-hydroxysteroid dehydrogenase 2 (HSD2). In the present study, we identified HSD2 neurons in the human brain, then used a mouse model to evaluate their role in aldosterone-induced salt intake. First, we confirmed that dietary sodium deprivation increases aldosterone production, salt intake, and HSD2 neuron activity. Next, we showed that continuous chemogenetic stimulation of HSD2 neurons causes a large and specific increase in salt intake. Finally, we use dose-response studies and genetically targeted ablation of HSD2 neurons to show that these neurons are necessary for aldosterone-induced salt intake. Identifying HSD2 neurons in the human brain and establishing their necessity for aldosterone-induced salt intake in mice improves our understanding of appetitive circuits and highlights this small cell population as a therapeutic target for moderating dietary sodium.

醛固酮诱导的盐食欲需要 HSD2 神经元。
醛固酮分泌过多会增加罹患心脏病、中风、痴呆症和死亡的风险。醛固酮会增加钠潴留和钠消耗,钠消耗增加可能会加重醛固酮增多症患者的内脏损害。防止这种增加可改善预后,但醛固酮诱导钠食欲的行为机制仍不清楚。在啮齿类动物中,我们先前发现了对醛固酮敏感的神经元,它们表达矿质皮质激素受体及其前受体调节剂--11-beta-羟基类固醇脱氢酶 2(HSD2)。在本研究中,我们鉴定了人脑中的 HSD2 神经元,然后利用小鼠模型评估了它们在醛固酮诱导的盐摄入中的作用。首先,我们证实了饮食中钠的剥夺会增加醛固酮的产生、盐的摄入和 HSD2 神经元的活性。接着,我们证明了对 HSD2 神经元的持续化学刺激会导致盐摄入量的大幅和特异性增加。最后,我们利用剂量反应研究和基因靶向消减 HSD2 神经元的方法证明,这些神经元是醛固酮诱导盐摄入的必要条件。鉴定人脑中的 HSD2 神经元并确定它们对小鼠醛固酮诱导的盐摄入的必要性,增进了我们对食欲回路的了解,并突出了这一小细胞群作为调节膳食钠的治疗靶点的重要性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
JCI insight
JCI insight Medicine-General Medicine
CiteScore
13.70
自引率
1.20%
发文量
543
审稿时长
6 weeks
期刊介绍: JCI Insight is a Gold Open Access journal with a 2022 Impact Factor of 8.0. It publishes high-quality studies in various biomedical specialties, such as autoimmunity, gastroenterology, immunology, metabolism, nephrology, neuroscience, oncology, pulmonology, and vascular biology. The journal focuses on clinically relevant basic and translational research that contributes to the understanding of disease biology and treatment. JCI Insight is self-published by the American Society for Clinical Investigation (ASCI), a nonprofit honor organization of physician-scientists founded in 1908, and it helps fulfill the ASCI's mission to advance medical science through the publication of clinically relevant research reports.
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