Sasaki K, Tooyama I, Li A J, Oomura Y, Kimura H
Division of Bio-Information Engineering, Faculty of Engineering, Toyama University, Japan.
Neuroscience. 1999;92(4):1287-94. doi: 10.1016/s0306-4522(99)00087-1.
We examined the effects of repeated subcutaneous injections of an acidic fibroblast growth factor fragment analog, [Ala16] acidic fibroblast growth factor (1-29), on learning and memory and on the choline acetyltransferase immunoreactivity of forebrain neurons in senescence-accelerated mice. One group of accelerated senescence-prone mice (accelerated senescence-prone-8) received [Ala16] acidic fibroblast growth factor (1-29), whereas the other group of accelerated senescence-prone-8 mice and a group of accelerated senescence-resistant mice (control) received vehicle solution. Injections began at three weeks after birth and were given weekly for 10 months. In a passive avoidance test, the mean retention latency at three, six and nine months of age was significantly longer in controls (vehicle-treated accelerated senescence-resistant-1) and acidic fibroblast growth factor fragment-treated accelerated senescence-prone-8 than in vehicle-treated accelerated senescence-prone-8 mice, and the latency in acidic fibroblast growth factor fragment-treated accelerated senescence-prone-8 mice was significantly shorter than that in controls only at nine months of age. In the Morris water maze task, the mean latency to climb onto the platform was significantly longer in acidic fibroblast growth factor fragment- and vehicle-treated accelerated senescence-prone-8 mice than in controls. However, the mean latency in the third and fourth trial blocks was significantly shorter for acidic fibroblast growth factor fragment-treated accelerated senescence-prone-8 than for vehicle-treated accelerated senescence-prone-8 mice. In the probe trials, controls and acidic fibroblast growth factor fragment-treated accelerated senescence-prone-8 mice spent significantly more time in the quadrant in which the platform had previously been located than in the other three quadrants. In acidic fibroblast growth factor fragment-treated accelerated senescence-prone-8 mice, the density of medial septum neurons intensely stained for choline acetyltransferase was significantly greater than that in vehicle-treated accelerated senescence-prone-8 mice, but significantly less than that in controls. The results indicate that the beneficial effect of [Ala16] acidic fibroblast growth factor (1-29) on learning and memory function in accelerated senescence-prone-8 mice may be related to a preservation of function in medial septum cholinergic neurons.
我们研究了重复皮下注射酸性成纤维细胞生长因子片段类似物[Ala16]酸性成纤维细胞生长因子（1-29）对衰老加速小鼠学习记忆及前脑神经元胆碱乙酰转移酶免疫反应性的影响。一组衰老加速易感性小鼠（衰老加速易感性-8）接受[Ala16]酸性成纤维细胞生长因子（1-29），而另一组衰老加速易感性-8小鼠和一组衰老抗性小鼠（对照组）接受溶剂。注射从出生后三周开始，每周注射一次，持续10个月。在被动回避试验中，对照组（溶剂处理的衰老抗性-1）和酸性成纤维细胞生长因子片段处理的衰老加速易感性-8小鼠在3个月、6个月和9个月龄时的平均记忆潜伏期明显长于溶剂处理的衰老加速易感性-8小鼠，且酸性成纤维细胞生长因子片段处理的衰老加速易感性-8小鼠仅在9个月龄时的潜伏期明显短于对照组。在莫里斯水迷宫任务中，酸性成纤维细胞生长因子片段和溶剂处理的衰老加速易感性-8小鼠爬上平台的平均潜伏期明显长于对照组。然而，酸性成纤维细胞生长因子片段处理的衰老加速易感性-8小鼠在第三和第四试验组的平均潜伏期明显短于溶剂处理的衰老加速易感性-8小鼠。在探索试验中，对照组和酸性成纤维细胞生长因子片段处理的衰老加速易感性-8小鼠在平台先前所在象限花费的时间明显多于其他三个象限。在酸性成纤维细胞生长因子片段处理的衰老加速易感性-8小鼠中，胆碱乙酰转移酶染色强烈的内侧隔区神经元密度明显高于溶剂处理的衰老加速易感性-8小鼠，但明显低于对照组。结果表明，[Ala16]酸性成纤维细胞生长因子（1-29）对衰老加速易感性-8小鼠学习记忆功能的有益作用可能与内侧隔区胆碱能神经元功能的保留有关。
