Role of Histaminergic Neurons in Brain-GUT Interactions

组胺能神经元在脑-肠胃相互作用中的作用

• 批准号: 11680778
• 负责人: FUKUDO Shin
• 金额: $ 2.11万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11680778/
• 关键词: brain-gut interactions; histamine; neurotransmitter; positron emission tomography; irritable bowel syndrome(IBS); corticotropin-releasing hormone(CRH); CRH-R1; noradrenaline; 脳波; 大脳誘発電位; 大腸運動

The aim of this study was to test the hypothesis that visceral stimulation induces neurotransmitter release, especially histamine, in the brain. The second hypothesis is that released histamine plays a role in modulating brain function. We expected that such analysis would result in identifying substance in brain-gut interactions. Microdilalysis experiment was performed using male Wistar rats. Colorectal distension of rats induced significant increase in histamine in the hippocampus from 1.34±0.47pmol/l to 4.68±0.58pmol/l (p<0.05). Anxiety-related behaviors were evoked when the rats were exposed to elevated plus maze after colorectal distention. Colorectal distention of rats also induced noradrenaline release in the hippocampus. These changes were blocked by administration of either non-specific corticotropin-releasing hormone (CRH) receptor antagonist α-helical CRH or specific CRH receptor-1 (CRH-R1) antagonist JTC017. In humans, positron emission tomography (PET) was performed for de … More tecting regional cerebral blood flow (rCBF) using H_2^<15>O which was synthesized with cyclotron. PET image under colonic distention was analyzed. Moreover, selective histamine H1 receptor antagonist d-chlorpheniramine was administered intravenously and PET image was analyzed. Colonic distention induced increase in rCBF in the thalamus, the anterior cingulate cortex, and the prefrontal cortex. Simultaneously, colonic distention inducedvisceral perception and emotion. These changes were significantly attenuated by administration and of d-chlorpheniramine. In patients with irritable bowel syndrome (IBS), left prefrontal cortex was activated. These results suggest that histamine noradrenaline, and CRH are released in the limbic system of the brain by colonic distention and that at least in part histamine H1 receptor and CRH-R1 are involved these phenomena. These results may open the door of possible therapeutic use of histamine H1 receptor antagonist or CRH-R1 antagonist for pathophysiological condition of brain-gut interactions. Less

本研究的目的是检验内脏刺激诱导神经递质释放的假设，特别是组胺，在大脑中。第二个假设是释放的组胺在调节脑功能中起作用。我们期望这样的分析将导致识别脑肠相互作用中的物质。采用雄性Wistar大鼠进行微透析实验。结直肠扩张引起大鼠海马组织中组胺含量从1.34±0.47pmol/L增加到4.68±0.58pmol/L（P<0.05）。结直肠扩张后，大鼠暴露于高架十字迷宫时，可诱发出行为学相关行为。大鼠结直肠扩张也诱导海马中去甲肾上腺素的释放。这些变化被非特异性促肾上腺皮质激素释放激素（CRH）受体拮抗剂α-螺旋CRH或特异性CRH受体-1（CRH-R1）拮抗剂JTC 017阻断。在人类中，正电子发射断层扫描（PET）被用于检测 ...更多信息 用回旋加速器合成的H_2^ O检测局部脑血流量（rCBF）<15>。分析结肠扩张状态下的PET图像。此外，静脉注射选择性组胺H1受体拮抗剂d-氯苯那敏，并分析PET图像。结肠扩张引起丘脑、前扣带皮层和前额叶皮层的rCBF增加。同时，结肠扩张引起内脏感觉和情绪。这些变化显着减弱管理和d-氯苯那敏。在肠易激综合征（IBS）患者中，左前额叶皮层被激活。这些结果表明，组胺，去甲肾上腺素，和CRH释放在大脑边缘系统的结肠扩张，并至少部分组胺H1受体和CRH-R1参与这些现象。这些结果可能为组胺H1受体拮抗剂或CRH-R1拮抗剂治疗脑-肠相互作用的病理生理状态打开了可能的大门。少

项目成果

Fukudo, S.et al.: "Positron emission tomography proved histamine release in the human brain in visceral perception and emotion"Psychosomatic Medicine. 61. 120-121 (1999)

Fukudo, S.等人：“正电子发射断层扫描证明了人脑内脏知觉和情绪中组胺的释放”心身医学。

Saito, K., et al.: "Colorectal distention induces hippocampal noradreneline release in rats : An in vivo microdialysis study"Brain Research. 947. 146-149 (2002)

Saito, K., 等人：“结肠直肠扩张诱导大鼠海马去甲肾上腺素释放：一项体内微透析研究”Brain Research。

Kano, M., et al.: "Specific brain processing of emotion by facial expressions in alexithymia : a H_2^<15>O-PET study"Brain. (in press). (2003)

Kano, M., et al.：“述情障碍中面部表情对情绪的特定大脑处理：一项 H_2^<15>O-PET 研究”Brain。

福土 審, 他: "過敏性腸症候群 心身症診断・治療ガイドライン2002"西間三馨監修,心身症の診断・治療ガイドライン作成とその実証的研究会作成協和企画,東京. 103-124(238) (2002)

Makoto Fukudo 等人：“肠易激综合征心身诊断和治疗指南 2002”，由 Mikaori Nishima 监督，由心身疾病诊断和治疗指南创建协会及其经验研究小组创建，Kyowa Kikaku，东京 103。 -124 (238) ) (2002)

Kano, M., et al.: "Specific brain processing of emotion by facial expressions in alexithymia: a H2^<15>O-PET study."Brain in press.

Kano, M., et al.：“述情障碍中面部表情对情绪的特定大脑处理：一项 H2^15O-PET 研究。”《大脑》正在出版。