Takeda Atsushi, Itoh Hiromasa, Tamano Haruna, Oku Naoto
Department of Medical Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, 52- 1 Yada, Shizuoka, 422-8526, Japan.
Biometals. 2006 Oct;19(5):565-72. doi: 10.1007/s10534-005-6145-9.
On the basis of the evidence of the enhanced susceptibility to kainate-induced seizures in young rats fed a zinc-deficient diet for 4 weeks, the relationship between zinc release from hippocampal neuron terminals and seizure susceptibility was studied in young rats fed the zinc-deficient diet for 2 weeks. Timm's stain, with which histochemically reactive zinc in the presynaptic vesicle is detected, was not attenuated in mossy fibers and other areas in the hippocampus after 2-week zinc deprivation, whereas the attenuation was observed after 4-week zinc deprivation. Extracellular zinc concentration was not also decreased after 2-week zinc deprivation, unlike the case after 4-week zinc deprivation. To check the capacity for zinc release from neuron terminals after 2-week zinc deprivation, the hippocampus was excessively stimulated with 100 mM KCl. The increase in extracellular zinc concentration of zinc-deficient group was significantly more than that of control group. These results suggest that zinc release from hippocampal neuron terminals is not affected by 2-week zinc deprivation. On the other hand, the latency in myoclonic jerks of zinc-deficient group was significantly shorter than in the control group after treatment with kainate, while the latency in clonic convulsions was not different between the two groups. Intracellular fura-2 signal, a calcium indicator, was significantly higher in the hippocampal CA3 areas of zinc-deficient group 4 s after delivery of kainate to dentate granule cells. These results suggest that susceptibility to kainate-induced seizures is altered prior to the decrease in extracellular zinc concentration and zinc release from neuron terminals in zinc-deficient young rats. The alteration of calcium signaling seems to be involved in the susceptibility in zinc deficiency.
基于给幼鼠喂食4周缺锌饮食后对海藻酸诱导的癫痫发作易感性增强的证据，研究了给幼鼠喂食2周缺锌饮食后海马神经元终末锌释放与癫痫发作易感性之间的关系。Timm染色可检测突触前囊泡中具有组织化学反应性的锌，在缺锌2周后，海马的苔藓纤维和其他区域的Timm染色并未减弱，而在缺锌4周后观察到了减弱。与缺锌4周后的情况不同，缺锌2周后细胞外锌浓度也没有降低。为了检测缺锌2周后神经元终末的锌释放能力，用100 mM KCl对海马进行过度刺激。缺锌组细胞外锌浓度的增加显著高于对照组。这些结果表明，缺锌2周不会影响海马神经元终末的锌释放。另一方面，用海藻酸处理后，缺锌组肌阵挛性抽搐的潜伏期明显短于对照组，而两组阵挛性惊厥的潜伏期没有差异。在向齿状颗粒细胞递送海藻酸4秒后，缺锌组海马CA3区的细胞内fura-2信号（一种钙指示剂）显著更高。这些结果表明，在缺锌幼鼠中，对海藻酸诱导的癫痫发作的易感性在细胞外锌浓度降低和神经元终末锌释放之前就发生了改变。钙信号的改变似乎与缺锌时的易感性有关。
