Study on Synaptic Plasticity in Aging Brain Tokyo Metropolitan Inst. Gerontology,

据推测，老化大脑的功能障碍是由于神经元丢失或突触密度降低而加速的。本研究的三个目的如下：1.研究与年龄相关的突触功能变化；3.检验防止突触密度下降是否可能延缓脑功能的下降。我们在以前的工作中发现，静息膜电位和Na/K-ATPase活性显著降低，这是一种突触功能障碍(Brain Res.，506：46-52,1989)。本研究证实，在衰老后期，突触膜上Na/K-ATPase的含量下降。其次，确定了四种新的神经节样蛋白作为神经细胞膜标记物。其中两个被指定为胆碱能神经元特异性抗原Chol-1，命名为GT1apha和GQ1balpha。另两个为O-乙酰化神经节苷脂O-Ac-GT3和O-Ac-GT2。后两者定位于树突状纤维的生长锥膜上。第三，在丰富的环境饲养条件下，大鼠的大脑得到了极大的发展。他们的记忆和学习能力等认知功能在成熟期比对照组得到了更好的改善，并在衰老过程中保持在与年轻阶段相同的水平。突触标志蛋白突触素的定量检测表明，丰富环境组突触密度明显高于对照组。这可能表明，通过增加突触密度可以预防或延缓因衰老而导致的脑功能障碍。

Dysfunction of aging brains is speculated to be accelerated by neuronal loss or diminished density of synapses. Three objectives of this study were as follows : 1. to examine the age-related changes of synaptic functions ; 3. to test whether the prevention of the decrement of synaptic density might retard the decreasing brain functions.We found significant decreases in resting membrane potential and in the activity of an electrogenic enzyme, Na/K-ATPase as a synaptic dysfunction in a previous work (Brain Res., 506 : 46-52, 1989). In this study, the cntent of Na/K-ATPase in synaptic membranes was proved to decrease in late senescence. Secondly, four new species of ganglioides were identified as neuronal membrane markers. Two of them were assigned as cholinergic neuron-specific antigens, Chol-1, and named GT1aalpha and GQ1balpha. Othe two were O-acetylated gangliosides, O-Ac-GT3 and O-Ac-GT2. The latter two were shown to be localized on the growth cone membranes of dendritic fibers. Thirdly, rat brains were demonstrated to greatly develop in rearing under enriched environment. Their cognitive functions such as memory and learning ability were better improved during maturation than control, and were maintained on a level with young stage during senescence. Quntitation of a synaptic marker protein, synaptophysin revealed that the synaptic density definitely increasedin enriched environmental group than in control. This may indicate the possibility that brain dysfunction due to aging could be prevented or retarded by increasing density of synapses.