Hellweg R, Fischer W, Hock C, Gage F H, Björklund A, Thoenen H
Max-Planck-Institute for Psychiatry, Clinical Institute, München, F.R.G.
Brain Res. 1990 Dec 24;537(1-2):123-30. doi: 10.1016/0006-8993(90)90348-f.
Nerve growth factor (NGF) and choline acetyltransferase (ChAT) activity levels were measured in 7 different brain regions in young (3-month-old) and aged (2-years-old) female Sprague-Dawley rats. Prior to analysis the spatial learning ability of the aged rats was assessed in the Morris' water maze test. In the aged rats a significant, 15-30%, increase in NGF levels was observed in 4 regions (septum, cortex, olfactory bulb and cerebellum), whereas the levels in hippocampus, striatum and the brainstem were similar to those of the young rats. The NGF changes did not correlate with the behavioral performance within the aged group. Minor 15-30%, changes in ChAT activity were observed in striatum, brainstem and cerebellum, but these changes did not correlate with the changes in NGF levels in any region. The results indicate that brain NGF levels are maintained at normal or supranormal levels in rats with severe learning and memory impairments. The results, therefore, do not support the view that the marked atrophy and cell loss in the forebrain cholinergic system that is known to occur in the behaviorally impaired aged rats is caused by a reduced availability of NGF in the cholinergic target areas. The results also indicate that the slightly increased levels of NGF are not sufficient to prevent the age-dependent atrophy of cholinergic neurons, although they might be important for the stimulation of compensatory functional changes in a situation where the system is undergoing progressive degeneration.
在年轻(3个月大)和老年(2岁)雌性Sprague-Dawley大鼠的7个不同脑区测量了神经生长因子(NGF)和胆碱乙酰转移酶(ChAT)的活性水平。在分析之前,通过莫里斯水迷宫试验评估老年大鼠的空间学习能力。在老年大鼠中,观察到4个脑区(隔区、皮质、嗅球和小脑)的NGF水平显著升高15 - 30%,而海马体、纹状体和脑干中的水平与年轻大鼠相似。老年组内NGF的变化与行为表现无关。在纹状体、脑干和小脑中观察到ChAT活性有轻微的15 - 30%的变化,但这些变化与任何脑区的NGF水平变化均无关联。结果表明,在有严重学习和记忆障碍的大鼠中,脑NGF水平维持在正常或超常水平。因此,这些结果不支持以下观点,即已知在行为受损的老年大鼠中发生的前脑胆碱能系统的明显萎缩和细胞丢失是由胆碱能靶区域NGF可用性降低所导致的。结果还表明,NGF水平的轻微升高不足以防止胆碱能神经元的年龄依赖性萎缩,尽管它们可能在刺激系统进行性退化时的代偿性功能变化中很重要。