NGF: A NEUROTROPHIC FACTOR FOR FOREBRAIN

这项提议将检验神经生长因子 神经生长因子(NGF)是胆碱能神经元的神经营养因子。 前脑。为了刻画NGF在体内的作用 这些细胞，P.I.已经发现NGF促进了 成年大鼠隔海马胆碱能神经元损伤后的变化 通过切断海马伞破坏它们的突起。 此外，初步研究结果表明，NGF刺激 胆碱能神经元在培养中的存活和纤维生长。 计划中的实验旨在彻底调查这些 NGF以前未被发现的影响，并在表征 它们发生的必要条件。将进行研究 在活体内，对患有隔膜损伤的年轻和老年成年大鼠- 海马胆碱能通路，以及体外培养的 胎鼠脑中的胆碱能神经元。此外，一个 免疫组织化学方法是最近由 P.I.用于显示大鼠大脑中的NGF受体。 到目前为止获得的发现，这些发现仅限于Telen-和 间脑，表明NGF受体被选择性地定位 前脑胆碱能神经元。计划中的实验旨在 证实了NGF受体和AT的选择性定位 区分胆碱能细胞和胆碱能细胞的定位 传入终末。此外，还建议对NGF进行映射 整个大鼠大脑中的受体。拟议的研究将会有所帮助。 确定NGF是否是前脑的神经营养因子 胆碱能神经元。此外，这些研究还具有重要意义。 治疗阿尔茨海默氏症，这种病与选择性丢失有关 在基底前脑的胆碱能神经元。建议数 研究涉及神经元群体的生存和功能 阿尔茨海默病的选择性影响和一种 这些神经元的神经营养因子。

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.