Takeda Atsushi, Itoh Hiromasa, Nagayoshi Akito, Oku Naoto
Department of Medical Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Shizuoka 422-8526, Japan.
Epilepsy Res. 2009 Jan;83(1):73-80. doi: 10.1016/j.eplepsyres.2008.09.009. Epub 2008 Nov 22.
On the basis of the evidence of the enhanced susceptibility to kainate-induced seizures in zinc-deficient mice and rats, the mechanism of the enhanced susceptibility was examined focused on neuronal Ca(2+) mobilization. Brain slices were prepared from rats fed a zinc-deficient diet for 4 weeks. Intracellular fura-2 signals in the hippocampal CA3, in which the basal fura-2 signals were higher in zinc deficiency, were significantly more increased 4s after delivery of kainate (1 mM/1 microl, 1 s) to the dentate granule cell layer. Calcium orange signal in mossy fiber boutons was also significantly more increased in zinc deficiency after delivery of tetanic stimuli (100 Hz, 5s) to the dentate granule cell layer in the presence of CNQX, a blocker of AMPA/kainate receptors. The decrease in FM4-64 signal, a direct measure of vesicular exocytosis, in mossy fiber boutons during tetanic stimulation (10 Hz, 180 s) was significantly enhanced in zinc deficiency. These results indicate that intracellular Ca(2+) mobilization in the hippocampus is affected in zinc deficiency, followed by the enhancement of exocytosis at mossy fiber boutons. In NMDA-challenged mice, which were fed the zinc-deficient diet for 4 weeks, furthermore, seizure susceptibility was significantly enhanced. It is likely that abnormal Ca(2+) mobilization in neurons is involved in seizure susceptibility in zinc-deficient animals.
基于锌缺乏的小鼠和大鼠对红藻氨酸诱导的癫痫发作易感性增强的证据，研究了这种易感性增强的机制，重点关注神经元的Ca(2+)动员。从喂食缺锌饮食4周的大鼠制备脑片。在向齿状颗粒细胞层递送红藻氨酸（1 mM/1微升，1秒）后4秒，锌缺乏时基础fura-2信号较高的海马CA3中的细胞内fura-2信号显著增加更多。在存在AMPA/红藻氨酸受体阻滞剂CNQX的情况下，向齿状颗粒细胞层递送强直刺激（100 Hz, 5秒）后，锌缺乏时苔藓纤维终扣中的钙橙信号也显著增加更多。在强直刺激（10 Hz, 180秒）期间，苔藓纤维终扣中FM4-64信号（囊泡胞吐作用的直接测量指标）的降低在锌缺乏时显著增强。这些结果表明，锌缺乏时海马中的细胞内Ca(2+)动员受到影响，随后苔藓纤维终扣处的胞吐作用增强。此外，在喂食缺锌饮食4周的NMDA激发的小鼠中，癫痫发作易感性显著增强。神经元中异常的Ca(2+)动员可能与锌缺乏动物的癫痫发作易感性有关。
