Markowska A L, Koliatsos V E, Breckler S J, Price D L, Olton D S
Department of Psychology, Johns Hopkins University, Baltimore, Maryland 21218-2686.
J Neurosci. 1994 Aug;14(8):4815-24. doi: 10.1523/JNEUROSCI.14-08-04815.1994.
The behavioral effects of human nerve growth factor (NGF) were assessed in Fischer-344 rats of two ages: 4 months old (4MO) and 23 months old (23MO). Recent memory was tested in delayed alteration (T maze), reference memory in a place discrimination (water maze), and sensorimotor skills in a battery of sensorimotor tasks. Each rat was preoperatively trained in each task, given either a control procedure (CON), or continuous infusion of human NGF via an osmotic minipump, and retested again 3 weeks later. Two doses of NGF were delivered: 40 micrograms and 160 micrograms (total amount infused over a period of 4 weeks). In 23MO-NGF rats, both doses improved performance in the recent memory task, and in some measures of the place learning task, but had no effect on sensorimotor skills. In 4MO-NGF rats, the low dose impaired performance in the recent memory task, but not in the place discrimination or in the sensorimotor tasks. These data indicate that human NGF can reverse age-related cognitive impairments in old rats. However, the present study also raises the issue of potential detrimental effects that NGF may exert in young normal subjects.
在4个月大（4MO）和23个月大（23MO）的Fischer-344大鼠中评估了人类神经生长因子（NGF）的行为效应。在延迟交替试验（T迷宫）中测试近期记忆，在位置辨别试验（水迷宫）中测试参考记忆，并在一系列感觉运动任务中测试感觉运动技能。每只大鼠在术前都接受了每项任务的训练，然后接受对照程序（CON），或通过渗透微型泵持续输注人类NGF，并在3周后再次进行测试。给予了两种剂量的NGF：40微克和160微克（在4周内输注的总量）。在23MO-NGF大鼠中，两种剂量均改善了近期记忆任务的表现以及位置学习任务的一些指标，但对感觉运动技能没有影响。在4MO-NGF大鼠中，低剂量损害了近期记忆任务的表现，但对位置辨别或感觉运动任务没有影响。这些数据表明，人类NGF可以逆转老年大鼠与年龄相关的认知障碍。然而，本研究也提出了NGF可能对年轻正常受试者产生潜在有害影响的问题。
