神经生长因子促进老年痴呆鼠学习记忆恢复和海马突触重建

切断老年鼠（２４月龄）左侧穹窿海马伞（ＦＦ），造成隔－海马胆碱能系统损伤的痴呆模型。用Ｍｏｒｒｉｓ水迷宫和体视学分析ＮＧＦ对模型鼠学习记忆和突触的影响。实验１个月后显示：（１）定位航行试验中，损伤组大鼠寻找平台的潜伏期，稳定后的平均值为４０ｓｅｃ，而ＮＧＦ治疗组为２２ｓｅｃ，相互间具有显著性差异（Ｐ＜０．０５）；（２）空间搜索试验中，损伤组在原平台象限跨越相应平台位置次数为１．９次，ＮＧＦ治疗组为５．９次，两者间有统计学意义（Ｐ＜０．０１）；（３）损伤组损伤侧齿状回分子层突触数密度和面密度分别下降２９％和１９．０３％，平均面积增大１１．４％。ＮＧＦ治疗组，突触数密度和面密度与损伤组相比，有显著升高（Ｐ＜０．０５），而平均面积显著下降（Ｐ＜０．０５），都接近于正常组；（４）损伤组损伤侧齿状回分子层突触前终末内线粒体的体密度和数密度分别下降３０．７％和５６．５％，体积增大３７．０９％。ＮＧＦ治疗组的体密度、数密度和体积与正常组相比，差异无显著性（Ｐ＞０．０５）。提示ＮＧＦ能够改善老年痴呆模型鼠学习记忆能力和促进海马突触重建。

NERVE GROWTH FACTOR IMPROVES THE ABILITY OF SPATIAL MEMORY AND SYNAPTIC REMODELLING IN AGED RATS WITH UNILATERAL FIMBRIA-FORNIX TRANSECTION

Aged male SD rats with left fimbria-fornix lesions received continuous infusion of NGF or Cyt. C into the cerebroventricular space.One month after lesion the animals were trained to find and then to retain the location of a hidden platform in the Morris water maze. Then electron microscopic study on synapse was performed in the molecular layer of dentate gyrus (MDG) of hippocampus. The results showed: (1 ) In place test, lesioned rats showed overall slower acquisition of the task,by the last 6 blocks of testing in a mean of 40 secs. Treated rats learned the task within 3 blocks of testing, and at the last 6 blocks of testing Teached the platform in a mean of 22 secs.The lesioned differed significantly from the treated(P<0.of);(2) In spatial probe test,the total numbers of crossing at the previous platform were 5. 9 for treated rats, 1.9 for lesioned ones.The lesioned differed significantly from the treated (P<0. 01);(3)A significant decrease of numerical(Nv)and surface(Sv) densities of the synaptic contact zones of MDG in lesioned rats vs,control ones(P<0. 01), Nv and Sv showed a mean decrease of 29 % and 19.03%.However,average area(S) of the synaptic contact zones was found to be significantly increased by 11.4%. Nv and Sv increased but S signifilantly decrease in treated rats vs,lesioned ones(P<0.05);(4)Asignificant decrease in mitochondrial volume density(Vv)and Nv of presynaptic terminals in MDG of lesioned rats vs, control ones(P<0.01),Vv and Nv showed a mean decrease of 30.77% and 56.59% Whereas the mitochondrial average volume(V)showed to be significantly increased by 37.09%.Mitochondrial Vv and Nv significantly increased(P<0.05),but V significantly decreased(P<0.05)in treated rats vs,lesioned ones.It suggests that NGF ameliorates spatial memory impairment and promotes synaptic remodelling in aged rats following lateral fimbrial lesion.