Brown C E, Dyck R H
Department of Psychology, University of Calgary, 2500 University Drive, NW, Calgary, Alberta, Canada, T2N 1N4.
Neuroscience. 2003;119(3):795-801. doi: 10.1016/s0306-4522(03)00292-6.
Zinc plays an important role in synaptic signaling in the mammalian cerebral cortex. Zinc is sequestered into presynaptic vesicles of subpopulations of glutamatergic neurons and is released by depolarization, in a calcium-dependent manner. As the majority of mechanisms that have been suggested to participate in experience-dependent alterations in synaptic strength in the cerebral cortex implicate signaling by glutamate, it stands to reason that zincergic signaling might also be crucial. Here we show that synaptic zinc is rapidly and dynamically modulated in relation to alterations in sensory input and that this response is highly age-dependent. Juvenile, adult, and aged mice were subjected to whisker removal and levels of staining for synaptic zinc in deprived and non-deprived cortical barrels were quantitatively assessed at post-deprivation times ranging from 3 h to 21 days. In the first 12 h, zinc levels increased slightly, but significantly, in all groups. At later time points, zinc levels increased robustly (23%) in the youngest group by 24 h and remained elevated through 7 days. By contrast, deprivation-induced changes in zinc staining in aged animals, achieved their maximal levels at 12 h (approximately 10%) and steadily declined thereafter. Adult animals revealed a biphasic, intermediate change with time. In all age groups, levels of zinc staining returned to baseline by 21 days after whisker plucking. However, only in juvenile and adult mice did we observe that the level of zinc staining in deprived barrel hollows, was correlated with the length of whiskers as they regrew. Our data suggest that alterations in the regulation of synaptic zinc may be involved with decrements of synaptic plasticity that accompany senescence.
锌在哺乳动物大脑皮层的突触信号传导中起着重要作用。锌被隔离在谷氨酸能神经元亚群的突触前囊泡中，并通过去极化以钙依赖的方式释放。由于大多数被认为参与大脑皮层突触强度经验依赖性改变的机制都涉及谷氨酸信号传导，因此锌信号传导也可能至关重要是合理的。在这里，我们表明突触锌会随着感觉输入的改变而迅速且动态地调节，并且这种反应高度依赖年龄。对幼年、成年和老年小鼠进行 whisker 去除，并在剥夺后 3 小时至 21 天的时间内定量评估剥夺和未剥夺的皮质桶中突触锌的染色水平。在最初的 12 小时内，所有组的锌水平均略有但显著升高。在随后的时间点，最年轻组的锌水平在 24 小时时强劲升高（23%），并在 7 天内一直保持升高。相比之下，老年动物中剥夺诱导的锌染色变化在 12 小时时达到最高水平（约 10%），此后稳步下降。成年动物随着时间呈现出双相的、中间的变化。在所有年龄组中，拔毛后 21 天锌染色水平恢复到基线。然而，只有在幼年和成年小鼠中，我们观察到剥夺桶状凹陷处的锌染色水平与重新生长的 whisker 长度相关。我们的数据表明，突触锌调节的改变可能与衰老伴随的突触可塑性降低有关。
