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Galanin与乙酰胆碱在 Septohappocampal途径，与学习，记忆和阿尔茨海默氏症有关 疾病。 加拉宁纤维和终端在 阿尔茨海默氏病的胆碱能基础前脑。 迈克·麦当劳（Mike McDonald）工作 在基础前脑中病变胆碱能神经元的病变条件 具有胆碱能选择性免疫毒素的大鼠，192igg-saporin，to 在延迟中产生胆碱能标记和缺陷 不匹配对大鼠的位置记忆任务，这类似于 那些在阿尔茨海默氏症的痴呆症中看到的。 今年，麦当劳博士完成了 Galanin，Galanin受体拮抗剂M40和 在 胆碱能病变模型。 初步数据表明组合 M1胆碱能激动剂的M40显着提高了性能 在病变的大鼠中。 这些发现表明Galanin过表达 可能导致痴呆症症状，而Galanin受体 拮抗剂可能是现有胆碱能的有用辅助疗法 治疗阿尔茨海默氏症的疗法。