Effects of an acidic fibroblast growth factor fragment analog on learning and memory and on medial septum cholinergic neurons ln senescence-accelerated mice

We examined the effects of repeated subcutaneous injections of an acidic fi broblast growth factor fragment analog, [Ala(16)] acidic fibroblast growth factor (1-29), on learning and memory and on the choline acetyltransferase immunoreactivity of forebrain neurons in senescence-accelerated mice. One g roup of accelerated senescence-prone mice (accelerated senescence-prone-8) received [Ala(16)] acidic fibroblast growth factor (1-29), whereas the othe r group of accelerated senescence-prone-8 mice and a group of accelerated s enescence-resistant mice (control) received vehicle solution. Injections be gan at three weeks after birth and were given weekly for 10 months. In a pa ssive avoidance test, the mean retention latency at three, six and nine mon ths of age was significantly longer in controls (vehicle-treated accelerate d senescence-resistant-1) and acidic fibroblast growth factor fragment-trea ted accelerated senescence-prone-8 than in vehicle-treated accelerated sene scence-prone-8 mice, and the latency in acidic fibroblast growth factor fra gment-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 accelerat ed senescence-prone-8 mice than in controls. However, the mean latency in t he third and fourth trial blocks was significantly shorter for acidic fibro blast growth factor fragment-treated accelerated senescence-prone-8 than fo r 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 wh ich the platform had previously been located than in the other three quadra nts. In acidic fibroblast growth factor fragment-treated accelerated senesc ence-prone-8 mice, the density of medial septum neurons intensely stained f or choline acetyltransferase was significantly greater than that in vehicle -treated accelerated senescence-prone-8 mice, but significantly less than t hat in controls. The results indicate that the beneficial effect of [Ala16] acidic fibroblas t growth factor(1-29) on learning and memory function in accelerated senesc ence-prone-8 mice may be related to a preservation of function in medial se ptum cholinergic neurons. (C) 1999 IBRO. Published by Elsevier Science Ltd.