O'Meara G, Coumis U, Ma S Y, Kehr J, Mahoney S, Bacon A, Allen S J, Holmes F, Kahl U, Wang F H, Kearns I R, Ove-Ogren S, Dawbarn D, Mufson E J, Davies C, Dawson G, Wynick D
Merck Sharp & Dohme Research Laboratories, Neuroscience Research Centre, Terlings Park, Harlow, CM20 2QR, United Kingdom.
Proc Natl Acad Sci U S A. 2000 Oct 10;97(21):11569-74. doi: 10.1073/pnas.210254597.
The neuropeptide galanin colocalizes with choline acetyltransferase, the synthetic enzyme for acetylcholine, in a subset of cholinergic neurons in the basal forebrain of rodents. Chronic intracerebroventricular infusion of nerve growth factor induces a 3- to 4-fold increase in galanin gene expression in these neurons. Here we report the loss of a third of cholinergic neurons in the medial septum and vertical limb diagonal band of the basal forebrain of adult mice carrying a targeted loss-of-function mutation in the galanin gene. These deficits are associated with a 2-fold increase in the number of apoptotic cells in the forebrain at postnatal day seven. This loss is associated with marked age-dependent deficits in stimulated acetylcholine release, performance in the Morris water maze, and induction of long-term potentiation in the CA1 region of the hippocampus. These data provide unexpected evidence that galanin plays a trophic role to regulate the development and function of a subset of septohippocampal cholinergic neurons.
神经肽甘丙肽与乙酰胆碱合成酶胆碱乙酰转移酶在啮齿动物基底前脑的一部分胆碱能神经元中共定位。慢性脑室内注入神经生长因子可使这些神经元中的甘丙肽基因表达增加3至4倍。在此，我们报告在甘丙肽基因中携带靶向功能丧失突变的成年小鼠基底前脑内侧隔区和垂直支斜角带中三分之一的胆碱能神经元缺失。这些缺陷与出生后第7天前脑凋亡细胞数量增加2倍有关。这种缺失与刺激的乙酰胆碱释放、莫里斯水迷宫中的行为表现以及海马体CA1区长期增强的诱导中明显的年龄依赖性缺陷有关。这些数据提供了意想不到的证据，表明甘丙肽在调节隔海马胆碱能神经元亚群的发育和功能中发挥营养作用。
