BRAIN/PELVIC VISCERA INTERACTIONS IN PSYCHIATRIC DISEASE

精神疾病中大脑/盆腔内脏的相互作用

• 批准号: 2688701
• 负责人: RITA VALENTINO
• 金额: $ 19.77万
• 依托单位: ALLEGHENY UNIVERSITY OF HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-05 至 1998-11-10
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2688701
• 关键词: chemical stimulation; colon; comorbidity; corticotropin releasing factor; electroencephalography; gastrointestinal function; gastrointestinal motility /pressure; immunocytochemistry; innervation; laboratory rat; locus coeruleus; mental disorders; neural transmission; neuroanatomy; neuroendocrine system; neuroregulation; prosencephalon; suid alphaherpesvirus 1; urinary bladder

DESCRIPTION: A striking feature of mood and anxiety disorders is their frequent coexistence with functional bowel disorders, such as irritable bowel syndrome. Conversely, psychiatric symptoms are prevalent in subjects diagnosed with functional bowel disorders, which occur in 10-20% of adults. These clinical observations implicate neural substrates linking the brain and gastrointestinal tract in pathology that is prevalent in the adult population. In the current application, a specific circuit linking the forebrain and gastrointestinal tract is proposed. It is proposed that Barrington's nucleus, via divergent projections to the brain noradrenergic nucleus, locus coeruleus (LC) and autonomic parasympathetic nuclei, is in a position to co-regulate brain noradrenergic activity and autonomic parasympathetic activity and thereby coordinate forebrain activity with gastrointestinal function. The proposed aims will provide anatomic and functional evidence for this hypothesis: The specific aims are: (1) Identify regions of the gastrointestinal tract that are linked to the LC via Barrington's nucleus. Transsynaptic tracing (using pseudorabies virus) from the colon, cecum and bladder will be combined with retrograde tract tracing from the LC to determine whether Barrington's LC-projecting neurons also project to preganglionic neurons innervating these organs; (2) Characterize the physiological impact of Barrington's sacral spinal-projections on colon function. Barrington's nucleus has been studied only with regard to its role in micturition. Its projections to the sacral parasympathetic nucleus suggest that it also regulates distal colon function. This hypothesis will be tested by characterizing the effects of selective chemical stimulation of Barrington's nucleus on colonic intraluminal pressure: (3) Determine the role of Barrington's LC-projections in arousal elicited by colon or bladder distension. Colon and bladder distension increase LC discharge and produce arousal as indicated by forebrain electroencephalographic (EEG) activation. The hypothesis that forebrain arousal elicited by colon or bladder distension is mediated by Barrington's projections to the LC will be determined using micro infusion of drugs to selectively inactivate the LC or Barrington's nucleus. Together, these AIMS will begin to elucidate the anatomy and functions of a novel circuit that it is in a position to coordinate forebrain and gastrointestinal activity; a circuit that could play a role in the prevalent disorders that are characterized by a coexistence of psychiatric and gastrointestinal symptoms.

说明： 情绪和焦虑症的一个显著特征是他们经常 与功能性肠病共存，如肠易激 综合症。相反，精神症状在受试者中普遍存在。 被诊断为功能性肠道疾病，这种疾病发生在10%-20%的成年人中。 这些临床观察表明神经底物连接大脑。 以及在成人中普遍存在的胃肠道 人口。在当前的应用中，一个特定的电路连接 提出了前脑和胃肠道的概念。现建议： 巴林顿核通过向脑去甲肾上腺素能的发散投射 蓝斑核团(LC)和自主副交感神经核团位于 共同调节大脑去甲肾上腺素能活动和自主神经的地位 副交感神经活动，从而协调前脑活动与 胃肠功能。拟议的目标将提供解剖和 支持这一假设的功能证据：具体目的是：(1) 确定胃肠道中通过以下途径与LC相连的区域 巴林顿核。跨突触追踪(使用伪狂犬病病毒) 结肠、盲肠、膀胱联合逆行示踪 以确定巴林顿的LC投射神经元是否也 投射到支配这些器官的节前神经元；(2)特征 巴林顿氏骶段脊髓投射对结肠的生理影响 功能。人们对巴灵顿核的研究仅限于它的 在排尿中的作用。其向骶骨副交感神经核的投射 提示它也调节远端结肠功能。这一假说将 通过表征选择性化学刺激的效果来测试 巴林顿核对结肠腔内压的影响：(3)测定 Barrington‘s LC投射在结肠或膀胱诱发觉醒中的作用 膨胀。结肠和膀胱扩张增加LC的排泄和产生 前脑脑电(EEG)激活表明的觉醒。 结肠或膀胱引起前脑兴奋的假说 扩张是由巴林顿对LC的预测调节的 使用微量输注药物选择性地灭活LC或 巴林顿核。综合起来，这些目标将开始阐明 一种新的电路的解剖和功能 协调前脑和胃肠道活动；一个可以 在流行的疾病中发挥作用，这些疾病的特征是 精神症状和胃肠道症状并存。