proBDNF对老龄鼠空间学习与记忆功能的影响

Effects of proBDNF on spatial learning and memory ability in aged mice

目的观察外源性proBDNF和内源性proBDNF对老龄鼠认知功能的影响。方法18月龄C57BL/6J鼠30只,随机分为3个组:proBDNF组、抗proBDNF组和对照组,分别采用微量渗透泵连续6d向右侧海马注射proBDNF、羊抗proBDNF或BSA,浓度均为1μg/μL,速度0.2μL/h。采用Morris水迷宫进行航行定位实验测定老龄鼠的平均逃避潜伏期、游泳速度,并进行空间探索实验测定动物在月台所在象限时间的百分比。结果Morris水迷宫实验第3天起,proBDNF注射组平均逃避潜伏期明显长于对照组;而抗proBDNF组平均逃避潜伏期比对照组短。各组之间游泳速度相差不显著。在空间探索实验中,proBDNF组在平台所在象限游泳时间的百分比明显比对照组小,动物入水后无目的游动,而抗proBDNF组在平台所在象限游泳时间的百分比明显比对照组增加,其运动轨迹主要集中于原平台所在位置。结论proBDNF能够降低老龄鼠的学习记忆功能,而阻断内源性proBDNF后能改善老龄鼠的学习记忆能力,提示proBDNF有着与成熟BDNF相反的功能。

Objective To observe the effects of exogenous and endogenous proBDNF on cognition function of aged mice. Methods Thirty 18-month-old C57BL/6J mice were randomly divided into three groups： proBDNF group,anti-proBDNF group,or bovine serum albumin （BSA） group. A Alzet osmotic minipump was connected to right hippocampus of the mouse. Pumps were filled with proBDNF （1μg/μL）, sheep antibody to proBDNF（1μg/μL）, or BSA （1μg/μL）, respectively. Mice received the injection for 6 days at the speed of 0.2μL/h. 21days after surgery,the animals were subjected for Morris Water Maze to test mean escape latency, swimming speed and percentage of time spent in the target quardrant. Results Compared with BSA control group,proBDNF group had longer mean escape latency （P（0.05） ,while the mean escape latency in antiproBDNF group was shorter（P〈0.05）. When it comes to swimming speed, there had no difference between each group. Compared with control group, mice in proBDNF group spent less time in the target quadrant,while mice in anti-proBDNF group spent more time in the target quadrant （P〈0.05）. Conclusion proBDNF can suppress the learning and memory ability of aged mice. It indicates that proBDNF plays a different role from that of mature BDNF.