ACIDIC FIBROBLAST GROWTH FACTOR AND BASAL FOREBRAIN

基底前脑胆碱能系统在脑内 认知功能，如记忆和注意力[8-13，48-49]，它 因此，胆碱能细胞尤其是 易受损伤和年龄相关的退化。 以前的研究 描述了神经生长因子（NGF），通过胆碱能细胞获得， 从皮质靶点逆行转运，作为 维持胆碱能神经元的活力。 最近的研究结果 然而，这个实验室和其他实验室表明， 内源性营养因子和存活之间的相互作用 胆碱能前脑系统 这个实验室已经证明了 存在高水平的酸性成纤维细胞生长因子mRNA （aFGF）定位于基底前脑的胆碱能细胞内。 这 发现沿着有报道称aFGF具有保护和 恢复胆碱能细胞的完整性[8]表明aFGF可能 作为胆碱能神经元的自分泌神经营养剂。 拟议 研究将进一步描述aFGF的分布及其 在胆碱能前脑系统的保护中的潜在作用。 具体而言，本研究旨在确定：（1）是否 合成aFGF的胆碱能神经元也表达FGF 因此，能够对这种保护性受体做出反应， 因素，（2）胆碱能神经元之间的解剖关系， 表达aFGF和对NGF有反应的那些;（3）如果表达 在前脑中发现的局部营养因子可能有助于维持 胆碱能细胞消融后的所有远距离营养支持，通过 兴奋性毒性损伤;和（4）检验aFGF的丧失 表达有助于基底前脑的年龄相关性变性 胆碱能神经元 拟议的研究应该进一步促进我们的 了解内源性营养支持提供给 前脑的胆碱能细胞，因此增强了我们的能力， 制定治疗策略，以对抗与年龄有关的退化 这个重要的大脑系统。

The basal forebrain cholinergic system plays an important role in cognitive functions such as memory and attention [8-13, 48-49], and it is therefore of great concern that cholinergic cells are particularly vulnerable to injury-and age-related degeneration. Previous research describes nerve growth factor (NGF), obtained by cholinergic cells via retrograde transport from cortical targets, as the critical substance in maintaining the viability of cholinergic neurons. Recent findings in this laboratory and others, however, indicate a much more complex interaction between endogenous trophic factors and the survival of the cholinergic forebrain system. This laboratory has demonstrated the existence of high levels of mRNA for acidic fibroblast growth factor (aFGF) localized within the cholinergic cells of basal forebrain. This finding along with reports that aFGF has a potent ability to protect and restore the integrity of cholinergic cells [8] suggests that aFGF may act as an autocrine neurotrophic for cholinergic neurons. The proposed research will further characterize the distribution of aFGF and its potential role in the preservation of the cholinergic forebrain system. Specifically, the aims of this study are to determine: (1) whether cholinergic neurons which synthesize aFGF are also expressing the FGF receptor and would therefore be capable of responding to this protective factor, (2) the anatomical relationship between cholinergic neurons which express aFGF and those which are responsive to NGF; (3) if the expression of local trophic factors identified in the forebrain may help sustain the cholinergic cells following ablation of all distant trophic support via excitotoxic lesion; and (4) to test the hypothesis that loss of aFGF expression contributes to age-related degeneration of the basal forebrain cholinergic neurons. The proposed research should further our understanding of the endogenous trophic support available to the cholinergic cells of the forebrain and therefore enhance our ability to develop therapeutic strategies for combating the age-related degeneration of this important brain system.