Suh S W, Jo S M, Vajda Z, Danscher G
Department of Neurobiology, Institute of Anatomy, University of Aarhus, DK-8000 Aarhus C, Denmark.
Brain Res. 2001 Mar 23;895(1-2):25-32. doi: 10.1016/s0006-8993(01)01996-5.
Chelatable zinc ions from synaptic vesicles have been suggested to be involved in neuronal death caused by stroke, epilepsy and head trauma. Elevated glucocorticoid concentration exacerbates such neuron loss, while low levels protect. We have tested the notion that the neuroprotective effect of prior glucocorticoid reduction is mediated by a reduction of zinc ions contained in zinc-enriched (ZEN) synaptic vesicles. The level of vesicular zinc ions was evaluated by toluene sulfonamide quinoline (TSQ) fluorometry and zinc autometallography (ZnS(AMG)) 10 and 30 days, respectively, after adrenalectomy. The hippocampus showed significant vesicular zinc ion depletion following adrenalectomy. After the kainate injection, adrenalectomized rats showed proconvulsive seizure behavior, i.e. shortened latency to seizure onset time and increased seizure score. Additionally they showed decreased hippocampal CA3 neuronal death as compared to control animals. The present data suggest that zinc ions released from damaged ZEN terminals are involved in seizure-induced neuronal death.
突触小泡中可螯合的锌离子被认为与中风、癫痫和头部创伤导致的神经元死亡有关。糖皮质激素浓度升高会加剧这种神经元损失，而低水平则具有保护作用。我们测试了先前糖皮质激素减少的神经保护作用是由富含锌（ZEN）的突触小泡中锌离子减少介导的这一观点。分别在肾上腺切除术后10天和30天，通过甲苯磺酰胺喹啉（TSQ）荧光测定法和锌自动金相术（ZnS(AMG)）评估囊泡锌离子水平。肾上腺切除术后海马体显示出明显的囊泡锌离子耗竭。注射红藻氨酸后，肾上腺切除的大鼠表现出惊厥前发作行为，即癫痫发作起始时间的潜伏期缩短和癫痫发作评分增加。此外，与对照动物相比，它们的海马体CA3神经元死亡减少。目前的数据表明，从受损的ZEN终末释放的锌离子参与了癫痫诱导的神经元死亡。
