BEHAVIORAL FUNCTIONS OF NEUROPEPTIDES

神经肽的行为功能

• 批准号: 6162858
• 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/6162858
• 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， 隔海马通路，与学习、记忆和阿尔茨海默病相关 疾病 甘丙肽纤维和终末在海马中过表达， 阿尔茨海默病患者的胆碱能基底前脑 迈克·麦克唐纳 基底前脑胆碱能神经元损伤的条件 大鼠注射胆碱能选择性免疫毒素192 IgG-saporin， 产生胆碱能标记物的损失和延迟 非匹配的位置记忆任务，这是类似于 与阿尔茨海默氏症中的相似。 今年，麦克唐纳博士完成了 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。 初步数据显示， M40与M1胆碱能激动剂联合使用可显著提高性能 在损伤的大鼠中。 这些发现表明甘丙肽过度表达 可能会导致痴呆症状，甘丙肽受体 拮抗剂可能是一种有用的辅助治疗现有的胆碱能 治疗阿尔茨海默氏症的方法。