Department of Neurophysiology, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan.
Int J Mol Sci. 2017 Nov 14;18(11):2411. doi: 10.3390/ijms18112411.
The basal levels of extracellular Zn are in the range of low nanomolar concentrations and less attention has been paid to Zn, compared to Ca, for synaptic activity. However, extracellular Zn is necessary for synaptic activity. The basal levels of extracellular zinc are age-dependently increased in the rat hippocampus, implying that the basal levels of extracellular Zn are also increased age-dependently and that extracellular Zn dynamics are linked with age-related cognitive function and dysfunction. In the hippocampus, the influx of extracellular Zn into postsynaptic neurons, which is often linked with Zn release from neuron terminals, is critical for cognitive activity via long-term potentiation (LTP). In contrast, the excess influx of extracellular Zn into postsynaptic neurons induces cognitive decline. Interestingly, the excess influx of extracellular Zn more readily occurs in aged dentate granule cells and intracellular Zn-buffering, which is assessed with ZnAF-2DA, is weakened in the aged dentate granule cells. Characteristics (easiness) of extracellular Zn influx seem to be linked with the weakened intracellular Zn-buffering in the aged dentate gyrus. This paper deals with the impact of synaptic Zn signaling on cognition and its decline in comparison with synaptic Ca signaling.
细胞外锌的基础水平处于低纳摩尔浓度范围内，与钙相比，人们对其在突触活动中的作用关注较少。然而，细胞外锌对于突触活动是必需的。在大鼠海马体中，细胞外锌的基础水平随年龄的增长而逐渐增加，这表明细胞外锌的基础水平也随年龄的增长而增加，并且细胞外锌的动态与与年龄相关的认知功能和功能障碍有关。在海马体中，细胞外锌流入突触后神经元的过程，通常与神经元末梢释放锌有关，通过长时程增强（LTP）对认知活动至关重要。相比之下，过量的细胞外锌流入突触后神经元会导致认知能力下降。有趣的是，过量的细胞外锌更容易进入老年齿状回颗粒细胞，并且在老年齿状回颗粒细胞中，用 ZnAF-2DA 评估的细胞内锌缓冲作用减弱。细胞外锌流入的特点（容易程度）似乎与老年齿状回中减弱的细胞内锌缓冲作用有关。本文比较了突触锌信号对认知及其衰退的影响与突触钙信号的影响。
