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急性和慢性抑制中枢 ghrelin 信号系统揭示了其在食物预期性活动中的作用。

Acute and chronic suppression of the central ghrelin signaling system reveals a role in food anticipatory activity.

机构信息

Rudolf Magnus Institute of Neuroscience, Department of Neuroscience and Pharmacology, University Medical Center Utrecht, Utrecht, The Netherlands.

出版信息

Eur Neuropsychopharmacol. 2011 May;21(5):384-92. doi: 10.1016/j.euroneuro.2010.06.005.

Abstract

Using the rodent activity-based anorexia (ABA) model that mimics clinical features of anorexia nervosa that include food restriction-induced hyperlocomotion, we found that plasma ghrelin levels are highly associated with food anticipatory behaviour, measured by running wheel activity in rats. Furthermore, we showed that ghrelin receptor (GHS-R1A) knockout mice do not anticipate food when exposed to the ABA model, unlike their wild type littermate controls. Likewise, food anticipatory activity in the ABA model was suppressed by a GHS-R1A antagonist administered either by acute central (ICV) injection to rats or by chronic peripheral treatment to mice. Interestingly, the GHS-R1A antagonist did not alter food intake in any of these models. Therefore, we hypothesize that suppression of the central ghrelin signaling system via GHS-R1A provides an interesting therapeutic target to treat hyperactivity in patients suffering from anorexia nervosa.

摘要

利用模拟神经性厌食症临床特征的啮齿动物活动性厌食(ABA)模型,包括食物限制引起的过度活动,我们发现血浆胃饥饿素水平与食物预期行为高度相关,这可以通过大鼠跑轮活动来测量。此外,我们表明,与野生型同窝对照相比,ghrelin 受体(GHS-R1A)敲除小鼠在暴露于 ABA 模型时不会预期食物。同样,通过急性中枢(ICV)注射大鼠或慢性外周治疗小鼠给予 GHS-R1A 拮抗剂可抑制 ABA 模型中的食物预期活动。有趣的是,GHS-R1A 拮抗剂在这些模型中均未改变食物摄入量。因此,我们假设通过 GHS-R1A 抑制中枢胃饥饿素信号系统为治疗神经性厌食症患者的过度活动提供了一个有趣的治疗靶点。

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