BEHAVIORAL FUNCTIONS OF NEUROPEPTIDES

神经肽甘丙肽与乙酰胆碱共存于 隔-海马区通路，与学习、记忆和阿尔茨海默病相关 疾病。甘丙氨酸纤维和终末在 阿尔茨海默病患者的胆碱能基底前脑。迈克·麦克唐纳工作了 损毁大鼠基底前脑胆碱能神经元的实验条件 胆碱选择性免疫毒素192Ig G-Saporin对大鼠 产生胆碱能标志物的丢失和迟发性脑缺血 大鼠的位置记忆任务不匹配，这类似于 那些在阿尔茨海默氏症中出现的。今年，麦克唐纳博士完成了 甘丙肽受体拮抗剂甘丙素、M40和 胆碱能药物和甘丙素化合物的组合，在 胆碱能损伤模型。初步数据显示，这种组合 使用M1胆碱能激动剂的M40显著提高了性能 在受损的老鼠身上。这些发现表明甘丙素过度表达 可能与痴呆症状有关，而甘丙肽受体 拮抗剂可能是现有胆碱能的有用的辅助治疗 治疗阿尔茨海默氏症的疗法。

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.