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To scratch an itch: Establishing a mouse model to determine active brain areas involved in acute histaminergic itch

机译:抓痒:建立小鼠模型以确定涉及急性组织胺能性瘙痒的活跃大脑区域

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BackgroundStrategies to efficiently control itch require a deep understanding of the underlying mechanisms. Several areas in the brain involved in itch and scratching responses have been postulated, but the central mechanisms that drive pruritic responses are still unknown. Histamine is recognized as a major mediator of itch in humans, and has been the most frequently used stimulus as an experimental pruritogen for brain imaging of itch.ObjectiveHistaminergic itchviahistamine and the selective histamine H4 receptor (H4R) agonist, ST-1006, recruit brain nuclei through c-fos activation and activate specific areas in the brain.MethodsAn acute itch model was established in c-fos-EGFP transgenic mice using ST-1006 and histamine. Coronal brain sections were stained for c-fos immunoreactivity and the forebrain was mapped for density of c-fos?+?nuclei.ResultsHistamine and ST-1006 significantly increased scratching response in c-fos-EGFP mice compared to vehicle controls. Mapping c-fos immunostained brain sections revealed neuronal activity in the cortex, striatum, hypothalamus, thalamus, amygdala, and the midbrain.ConclusionsHistaminergic itch and selective H4R activation significantly increased the density of c-fos?+?nuclei in the medial habenula (MHb). Thus, the MHb may be a new target to investigate and subsequently develop novel mechanism-based strategies to treat itch and possibly provide a locus for pharmacological control of pruritus.
机译:背景有效控制瘙痒的策略需要对潜在机制的深刻理解。已经假定了大脑中涉及瘙痒和抓挠反应的几个区域,但是驱动瘙痒反应的中心机制仍然未知。组胺被认为是人类瘙痒的主要介质,并且是刺激性的用于脑痒成像的实验性促红素原。目的组胺能itchviahistamine和选择性组胺H4受体(H4R)激动剂ST-1006可募集脑核。方法利用ST-1006和组胺在c-fos-EGFP转基因小鼠中建立急性瘙痒模型。对冠状脑切片进行c-fos免疫反应染色,并绘制前脑的c-fosα+α核密度。结果与载体对照相比,组胺和ST-1006显着增加了c-fos-EGFP小鼠的抓挠反应。绘制c-fos免疫染色的大脑切片的图谱显示了大脑皮层,纹状体,下丘脑,丘脑,杏仁核和中脑的神经元活动。 )。因此,MHb可能是研究并随后开发基于新机制的策略治疗瘙痒的新靶点,并可能为瘙痒的药理控制提供一个场所。

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