Brain activation in response to visceral stimulation in rats with amygdala implants of corticosterone: an FMRI study.
Brain activation in response to visceral stimulation in rats with amygdala implants of corticosterone: an FMRI study.
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DOI：
10.1371/journal.pone.0008573
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发表时间：
2010-01-05
期刊：
影响因子：
3.7
通讯作者：
Greenwood-Van Meerveld B
中科院分区：
文献类型：
--
作者：
Johnson AC;Myers B;Lazovic J;Towner R;Greenwood-Van Meerveld B
虽然胃肠道（GI）源性内脏疼痛是肠易激综合征（IBS）患者的主要主诉，但人们对它的了解仍然很少。脑成像研究表明，肠易激综合征患者的脑肠通讯存在缺陷，包括杏仁核在内的中枢唤醒回路的激活程度更高。先前，我们发现立体定向植入皮质酮（CORT）在大鼠的杏仁核诱导焦虑和结肠过敏。在本研究中，我们使用功能性磁共振成像（fMRI）来识别以焦虑和结肠过敏为特征的大鼠模型中激活的特定脑部位。麻醉后的雄性大鼠在每个杏仁核背缘立体定向植入CORT或胆固醇（CHOL）微球（每个30µg）作为对照。7天后，麻醉大鼠，置于fMRI （7T）磁体中。采用标准块组设计，在两种压力（40和60 mmHg）下进行一系列等压结肠球囊扩张（CRD - 90“关”，30“开”，8个重复）。使用交叉相关统计分析来确定CORT和cholo处理动物的肿胀和非肿胀状态之间的显著差异。成像数据分析显示，与CHOL对照组相比，植入CORT的大鼠对CRD的整体大脑激活程度更高。此外，CORT植入物对特定核（焦虑和疼痛感知中重要的整合部位）的CRD反应产生了显著的双侧阳性MRI信号增加。这些数据表明，杏仁核长期暴露在高水平的CORT下，会增强大脑对CRD的整体激活，并确定了其他特定的大脑区域，会对结肠的机械膨胀做出反应。这些结果证明了在啮齿动物模型中进行功能磁共振成像的可行性，支持了对具有增强杏仁核激活和腹痛和焦虑症状的IBS患者的临床观察。
Although visceral pain of gastrointestinal (GI) origin is the major complaint in patients with irritable bowel syndrome (IBS) it remains poorly understood. Brain imaging studies suggest a defect in brain-gut communication in IBS with a greater activation of central arousal circuits including the amygdala. Previously, we found that stereotaxic implantation of corticosterone (CORT) onto the amygdala in rats induced anxiety and colonic hypersensitivity. In the present study we used functional magnetic resonance imaging (fMRI) to identify specific brain sites activated in a rat model characterized by anxiety and colonic hypersensitivity. Anesthetized male rats received micropellets (30 µg each) of either CORT or cholesterol (CHOL), to serve as a control, implanted stereotaxically on the dorsal margin of each amygdala. Seven days later, rats were anesthetized and placed in the fMRI magnet (7T). A series of isobaric colorectal balloon distensions (CRD - 90s ‘off’, 30s ‘on’, 8 replicates) at two pressures (40 and 60 mmHg) were performed in a standard block-design. Cross correlation statistical analysis was used to determine significant differences between distended and non-distended states in CORT and CHOL-treated animals. Analysis of the imaging data demonstrated greater overall brain activation in response to CRD in rats with CORT implants compared to CHOL controls. Additionally, CORT implants produced significant positive bilateral increases in MRI signal in response to CRD in specific nuclei known as integration sites important in anxiety and pain perception. These data indicate that chronic exposure of the amygdala to elevated levels of CORT enhances overall brain activation in response to CRD, and identified other specific brain regions activated in response to mechanical distension of the colon. These results demonstrate the feasibility of performing fMRI imaging in a rodent model that supports clinical observations in IBS patients with enhanced amygdala activation and symptomatology of abdominal pain and anxiety.
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影响因子：
24.5
作者：
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通讯作者：
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