BEHAVIORAL FUNCTIONS OF NEUROPEPTIDES

神经肽的行为功能

• 批准号: 6290527
• 负责人: Jacqueline N Crawley
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF MENTAL HEALTH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6290527
• 关键词: acetylcholine; central neural pathway /tract; dementia; disease /disorder model; dopamine; experimental brain lesion; galanin; immunoconjugates; laboratory rat; neurochemistry; neuropharmacology; psychomotor function

The neuropeptide galanin coexists with acetylcholine in the rat septohippocampal pathway, relevant to learning and memory, and is overexpressed in the basal forebrain in Alzheimers disease. We discovered that galanin administration to rats impairs performance on several memory tasks. Last year, postdoctoral fellow Mike McDonald demonstrated that the galanin receptor antagonist, M40, potentiated the beneficial actions of an M-1 muscarinic agonist, TZTP, in rats with 192-IgG saporin cholinergic lesions, on delayed nonmatching to position. These findings support an inhibitory modulatory role for endogenous galanin in modulating cholinergic pathways necessary for memory processes, and indicate that galanin antagonists may be a useful adjunct therapy to existing cholinergic therapies for treating Alzheimers dementia. PUBLICATION: McDonald, Willard, Wenk, Crawley, Coadministration of a galanin antagonist M40 with a muscarinic M1 agonist improved delayed nonmatching to position in rats with choinergic lesions. Journal of Neuroscience 18: 5-78-5085, 1998.Postdoctoral fellow Terri Gleason set up the Morris water task last year, to test the actions of galanin in this widely used memory test. Intraventricularly administered galanin induced performance deficits on latency to find the hidden platform over training trials, and on selective quadrant search during the probe trial. Significant genetic components were detected in responsiveness to galanin. The Wistar and Sprague-Dawley strains were sensitive to the inhibitory actions of galanin, as compared to the Long-Evans strain which was unaffected by galanin treatment in this task. Performance on the visible platform task and in Digiscan exploratory locomotion was normal at doses of galanin which impaired acquisition of the Morris water task. PUBLICATION: Gleason, Dreiling and Crawley, Rat strain differences in response to galanin on the Morris water task. Neuropeptides, in press, 1999.This year our galanin research program received a new research tool. Galanin overexpressing transgenic mice were generated by Robert Steiner and coworkers at the University of Washington, Seattle, and backcrossed for 7 generations into a C57BL/6J background for our behavioral experiments. Postdoctoral fellow Andrew Holmes and several student volunteers conducting the first behavioral phenotyping on galanin transgenic mice and their wild type control littermates. General health, home cage behaviors, neurological reflexes, and motor functions were normal. Impaired performance on several memory tasks was detected in the first pilot studies, primarily in the male transgenics. Experiments employing additional memory tasks, behavioral tests addressing the domains of feeding, analgesia, and anxiety, are now ongoing. - neuropeptides behavior galanin acetylcholine memory Alzheimer's disease

神经肽Galanin与大鼠Septohappocampal途径中的乙酰胆碱并存，与学习和记忆有关，并且在阿尔茨海默氏病的基础前脑中过表达。我们发现Galanin对大鼠的管理会损害多个记忆任务的性能。去年，博士后同伴迈克·麦克唐纳（Mike McDonald）证明，Galanin受体拮抗剂M40增强了M-1毒蕈碱激动剂TZTP在192-IGG Saporin胆碱能病变中的有益作用，在延迟的无抗位置上。这些发现支持内源性甘氨酸在调节记忆过程所需的胆碱能途径中的抑制作用调节作用，并表明Galanin拮抗剂可能是治疗阿尔茨海默氏症治疗胆碱能疗法的有用辅助治疗。出版物：麦当劳，威拉德，温克，克劳利，加拉宁拮抗剂M40与毒蕈碱M1激动剂共同给药，改善了延迟的不匹配，以在患有Choinergic病变的大鼠中的位置。神经科学杂志18：5-78-5085，1998。脑室室内给药的Galanin引起的延迟诱发性能缺陷，以在训练试验中找到隐藏的平台，以及在探针试验期间选择性象限搜索。在对加拉宁的反应中检测到了重要的遗传成分。与长期埃文斯菌株相比，Wistar和Sprague-Dawley菌株对Galanin的抑制作用敏感，而在此任务中不受Galanin处理的影响。可见的平台任务和Digiscan探索性运动的性能在Galanin的剂量下正常，这损害了莫里斯水务任务的收购。出版物：格里森，德雷里和克劳利，对莫里斯水务任务的对加拉宁的响应师菌株差异。神经肽，在出版社，1999年。我们的加拉宁研究计划获得了新的研究工具。华盛顿大学的罗伯特·斯坦纳（Robert Steiner）和西雅图大学（University of Washington）的罗伯特·施泰纳（Robert Steiner）和同事产生了甘岩蛋白过表达的转基因小鼠，并在我们的行为实验中进行了7代人的回纹。博士后安德鲁·福尔摩斯（Andrew Holmes）和几位学生志愿者对加拉蛋白转基因小鼠及其野生型控制同窝仔进行第一次行为表型。一般健康，家庭笼行为，神经反射和运动功能正常。在第一批试点研究中检测到了几个记忆任务的性能受损，主要是在男性转基因中。现在正在进行采用其他记忆任务，解决喂养，镇痛和焦虑领域的行为测试的实验。 - 神经肽行为甘氨酸乙酰胆碱记忆阿尔茨海默氏病