BEHAVIORAL FUNCTIONS OF NEUROPEPTIDES

神经肽的行为功能

• 批准号: 6111124
• 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/6111124
• 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 septohippocampal pathway, relevant to learning, memory, and Alzheimer's disease. Galanin fibers and terminals are overexpressed in the cholinergic basal forebrain in Alzheimer's disease. Mike McDonald worked out conditions for lesioning cholinergic neurons in the basal forebrain of the rat with the cholinergically selective immunotoxin, 192IgG-saporin, to produce a loss of cholinergic markers and deficits in the delayed non-matching to position memory task in rats, which were analogous to those seen in Alzheimer's dementia. This year, Dr. McDonald completed experiments with galanin, the galanin receptor antagonist, M40, and combinations of cholinergic drugs and galanin compounds, in the cholinergic lesion model. Preliminary data indicate that the combination of M40 with an M1 cholinergic agonist significantly improves performance in the lesioned rats. These findings indicate that galanin overexpression may contribute to the dementia symptoms, and that galanin receptor antagonists may be a useful adjunct therapy to existing cholinergic therapies for treating Alzheimer's dementia.

神经肽甘丙肽与乙酰胆碱共存于 隔海马通路，与学习、记忆和阿尔茨海默病相关 疾病。 甘丙肽纤维和末端在 阿尔茨海默病中的胆碱能基底前脑。 迈克·麦克唐纳工作过 损害基底前脑胆碱能神经元的条件 使用胆碱能选择性免疫毒素 192IgG-皂草素的大鼠 产生胆碱能标记物的损失和延迟的缺陷 与大鼠的位置记忆任务不匹配，类似于 那些在阿尔茨海默氏痴呆症中看到的。 今年，麦克唐纳博士完成了 使用甘丙肽、甘丙肽受体拮抗剂 M40 和 胆碱能药物和甘丙肽化合物的组合， 胆碱能损伤模型。 初步数据表明，该组合 M40 与 M1 胆碱能激动剂显着提高性能 在受损的老鼠中。 这些发现表明甘丙肽过度表达 可能会导致痴呆症状，而甘丙肽受体 拮抗剂可能是现有胆碱能药物的有用辅助治疗 治疗阿尔茨海默氏痴呆症的疗法。