Schmoll H, Ramboiu S, Platt D, Herndon J G, Kessler Ch, Popa-Wagner A
Department of Neurology, Ernst Moritz Arndt University, Greifswald, Germany.
Gerontology. 2005 Jul-Aug;51(4):215-24. doi: 10.1159/000085117.
Normal aging is associated with impairments in learning and memory and motor function. One viable hypothesis is that these changes reflect an age-related decrease in brain plasticity.
The aim of the present study was to identify age-related changes in the time course of expression of the axonal growth associated protein 43 (GAP-43) in a rat model of brain plasticity.
We examined by Northern blotting, in situ hybridization, and immunohistochemistry the effects of age on the time course of the expression GAP-43 following pentylenetetrazole-induced seizure in the hippocampus of 3-, 18-, and 28-month-old rats.
In this model of brain plasticity, young rats displayed a decrease in GAP-43 mRNA levels in CA1, CA3, and polymorphic regions, lasting from 10 h to 3 days after seizure. This was followed by recovery, with peak expression between days 10 and 20. The baseline levels of GAP-43 mRNA decreased with age, especially in the CA3 region. Despite lower baseline levels, middle-aged rats showed the same pattern of upregulation of GAP-43 mRNA expression as the young animals. Old rats showed only minimal upregulation, however, and this occurred only in the polymorphic layer. The level GAP-43 protein itself was higher in old control rats than in the other two control groups, a condition that was transiently reversed by seizure activity.
Middle-aged rats are still capable of a sustained, though diminished, response to seizure activity, while old rats lose this ability. Disruption of the temporal and anatomical coordination of expression of GAP-43 may contribute to the general decline in brain plasticity with age.
正常衰老与学习记忆及运动功能受损有关。一种可行的假说是，这些变化反映了与年龄相关的大脑可塑性下降。
本研究旨在确定在大脑可塑性大鼠模型中，轴突生长相关蛋白43（GAP - 43）表达的时间进程中与年龄相关的变化。
我们通过Northern印迹法、原位杂交和免疫组织化学，研究了年龄对3个月、18个月和28个月大的大鼠海马体中戊四氮诱导癫痫发作后GAP - 43表达时间进程的影响。
在这个大脑可塑性模型中，幼鼠在癫痫发作后10小时至3天内，CA1、CA3和多形区的GAP - 43 mRNA水平下降。随后恢复，在第10天至20天达到表达峰值。GAP - 43 mRNA的基线水平随年龄下降，尤其是在CA3区。尽管基线水平较低，但中年大鼠GAP - 43 mRNA表达上调模式与幼鼠相同。然而，老年大鼠仅表现出最小程度的上调，且仅发生在多形层。老年对照大鼠的GAP - 43蛋白水平本身高于其他两个对照组，癫痫活动可短暂逆转这种情况。
中年大鼠对癫痫活动仍能产生持续但减弱的反应，而老年大鼠则丧失了这种能力。GAP - 43表达的时间和解剖协调性破坏可能导致大脑可塑性随年龄普遍下降。
