Steiner R A, Hohmann J G, Holmes A, Wrenn C C, Cadd G, Juréus A, Clifton D K, Luo M, Gutshall M, Ma S Y, Mufson E J, Crawley J N
Department of Obstetrics and Gynecology, University of Washington, Seattle, WA 98195-7290, USA.
Proc Natl Acad Sci U S A. 2001 Mar 27;98(7):4184-9. doi: 10.1073/pnas.061445598. Epub 2001 Mar 20.
Galanin is a neuropeptide with multiple inhibitory actions on neurotransmission and memory. In Alzheimer's disease (AD), increased galanin-containing fibers hyperinnervate cholinergic neurons within the basal forebrain in association with a decline in cognition. We generated transgenic mice (GAL-tg) that overexpress galanin under the control of the dopamine beta-hydroxylase promoter to study the neurochemical and behavioral sequelae of a mouse model of galanin overexpression in AD. Overexpression of galanin was associated with a reduction in the number of identifiable neurons producing acetylcholine in the horizontal limb of the diagonal band. Behavioral phenotyping indicated that GAL-tgs displayed normal general health and sensory and motor abilities; however, GAL-tg mice showed selective performance deficits on the Morris spatial navigational task and the social transmission of food preference olfactory memory test. These results suggest that elevated expression of galanin contributes to the neurochemical and cognitive impairments characteristic of AD.
甘丙肽是一种对神经传递和记忆具有多种抑制作用的神经肽。在阿尔茨海默病（AD）中，含甘丙肽纤维增多会过度支配基底前脑内的胆碱能神经元，同时认知功能下降。我们构建了在多巴胺β-羟化酶启动子控制下过表达甘丙肽的转基因小鼠（GAL-tg），以研究AD中甘丙肽过表达小鼠模型的神经化学和行为后遗症。甘丙肽过表达与斜角带水平支中可识别的乙酰胆碱产生神经元数量减少有关。行为表型分析表明，GAL-tg小鼠的一般健康状况以及感觉和运动能力正常；然而，GAL-tg小鼠在莫里斯空间导航任务和食物偏好嗅觉记忆测试的社会传递方面表现出选择性缺陷。这些结果表明，甘丙肽表达升高会导致AD特有的神经化学和认知障碍。
