ACIDIC FIBROBLAST GROWTH FACTOR AND BASAL FOREBRAIN

基底前脑胆碱能系统在 认知功能，如记忆和注意力[8-13，48-49]，以及它 因此，胆碱能细胞尤其令人担忧 易受损伤和年龄相关的退化的影响。以前的研究 描述了神经生长因子(NGF)，由胆碱能细胞通过 皮质靶的逆行转运，作为体内的关键物质 维持胆碱能神经元的活性。的最新发现 然而，这个实验室和其他实验室表明， 内源营养因子之间的相互作用与水母的生存 胆碱能前脑系统。这个实验室已经证明了 酸性成纤维细胞生长因子基因的高水平表达 (AFGF)定位于基底前脑的胆碱能细胞。这 与报告一起发现aFGF具有强大的保护和 恢复胆碱能细胞的完整性[8]表明a成纤维细胞可能起作用 作为胆碱能神经元的自分泌神经营养物质。建议数 研究将进一步确定a成纤维细胞生长因子的分布及其 保护胆碱能前脑系统的潜在作用。 具体地说，本研究的目的是确定：(1)是否 合成成纤维细胞生长因子的胆碱能神经元也表达成纤维细胞生长因子 受体，因此能够对这种保护性 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 切除所有远端营养支持后的胆碱能细胞 兴奋性毒性损伤；以及(4)检验aFGFs丢失的假设 表达与年龄相关的基底前脑退行性变有关 胆碱能神经元。拟议的研究应该会进一步推动我们的 对内源性营养支持的理解 前脑的胆碱能细胞，从而增强我们的能力 制定抗击年龄相关性退行性变的治疗策略 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.