NGF: A NEUROTROPHIC FACTOR FOR FOREBRAIN

这项提议将检验神经生长因子 (NGF)是一种胆碱能神经元的神经营养因子， 前脑 在试图描述神经生长因子对 这些细胞私家侦探发现神经生长因子能促进 吗啡对成年大鼠隔-海马胆碱能神经元的影响 通过切断菌毛破坏其突起。 此外，初步研究结果表明，NGF刺激 培养胆碱能神经元存活和纤维生长。 计划中的实验旨在彻底调查这些 以前未发现的影响，神经生长因子和表征 这是它们发生的必要条件。 研究将进行 在体内，对年轻和年老的成年大鼠与病变的隔- 海马胆碱能通路，并在体外，对培养 来自胎鼠脑的胆碱能神经元。 此外， 免疫组织化学方法最近已由 P.I. 用于观察大鼠大脑中的神经生长因子受体。 迄今为止获得的调查结果，仅限于telen和 间脑，表明神经生长因子受体的选择性定位 对前脑胆碱能神经元的影响 计划中的实验旨在 证实了NGF受体的这种选择性定位， 区分胆碱能细胞中的定位和 传入末梢 此外，建议映射NGF 感受器。 拟议的研究将有助于 以确定NGF是否是前脑的神经营养因子 胆碱能神经元 此外，这些研究还具有影响 老年痴呆症与选择性丧失 基底前脑胆碱能神经元。 拟议 研究关注神经元群体的存活和功能 选择性影响阿尔茨海默病和影响的一个 神经营养因子的作用。

This proposal will test the hypothesis that nerve growth factor (NGF) is a neurotrophic factor for cholinergic neurons of the forebrain. In an attempt to characterize the actions of NGF on these cells, the P.I. has found that NGF promotes survival of cholinergic septo-hippocampal neurons of adult rats after destruction of their processes by transection of the fimbria. Furthermore, preliminary findings indicate that NGF stimulates survival and fiber growth of cholinergic neurons in culture. Planned experiments aim at thoroughly investigating these previously undiscovered effects of NGF and at characterizing the conditions necessary for them to occur. Studies will be carried out in vivo, on young and aged adult rats with lesions of the septo- hippocampal cholinergic pathway, and in vitro, on cultured cholinergic neurons from fetal rat brains. In addition, an immunohistochemical method has recently been developed by the P.I. for the visualization of NGF receptors in the rat brain. Findings obtained so far, and which were limited to telen- and diencephalon, indicate that NGF receptors are selectively located on forebrain cholinergic neurons. Planned experiments aim at substantiating this selective localization of NGF receptors and at differentiating between a localization in cholinergic cells and afferent terminals. Furthermore, it is proposed to map NGF receptors in the entire rat brain. The proposed studies will help to establish whether NGF is a neurotrophic factor for forebrain cholinergic neurons. Furthermore, the studies have implications for Alzheimer's disease which is associated with a selective loss of cholinergic neurons in the basal forebrain. The proposed studies concern survival and function of a neuronal population selectively affected in Alzheimer's disease and the effects of a neurotrophic factor for these neurons.