Cytosolic labile zinc accumulation in degenerating dopaminergic neurons of mouse brain after MPTP treatment
Cytosolic labile zinc accumulation in degenerating dopaminergic neurons of mouse brain after MPTP treatment
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DOI：
10.1016/j.brainres.2009.06.046
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发表时间：
2009-08-25
期刊：
影响因子：
2.9
通讯作者：
Koh, Jae-Young
中科院分区：
文献类型：
--
作者：
Lee, Joo-Yong;Son, Hyo Jin;Koh, Jae-Young
脑损伤后，如缺血性中风、外伤、癫痫和低血糖，在退化的神经元中积累高水平的不稳定锌。在发育过程中或神经元靶消融后发生凋亡的脑神经元中也发现了胞质锌积累。因此，锌特异性探针染色可用于识别脑内神经元死亡。在这项研究中，小鼠腹腔注射4次20 mg/kg剂量的1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP），间隔2小时，然后评估多巴胺能神经元的锌积累和凋亡。在致密黑质中，锌特异性荧光染料显示，通过末端脱氧核苷酸转移酶介导的dutp -生物素镍端标记（TUNEL）或酸性品红或Fluoro-Jade C染色鉴定的所有变性神经元含有高水平的胞质不稳定锌。多巴胺能神经元胞浆内锌积累，细胞核凝聚/断裂，提示凋亡细胞死亡。这些发现支持了这样的假设，即细胞内不稳定的锌积累是帕金森病动物模型中多巴胺能神经元退化的一个指标。(C) 2009 Elsevier B.V.版权所有
High levels of labile zinc accumulate in degenerating neurons after brain injury, such as ischemic stroke, trauma, epilepsy, and hypoglycemia. Cytosolic zinc accumulation is also found in brain neurons undergoing apoptosis during development or after neuronal target ablation. Thus, staining with zinc-specific probes can be used to identify neuronal death in the brain. In this study, mice were intraperitoneally given four 20 mg/kg doses of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) at 2-hour intervals, and dopaminergic neurons were then evaluated for zinc accumulation and apoptosis. In the substantia nigra pars compacta, zinc-specific fluorescent dyes revealed that all degenerating neurons, identified by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling (TUNEL), or acid fuchsin or Fluoro-Jade C staining, contained high levels of cytosolic labile zinc. Nuclear condensation/fragmentation was noted in dopaminergic neurons with cytosolic zinc accumulation, indicating apoptotic cell death. These findings support the supposition that cytosolic labile zinc accumulation is an indicator of degenerating dopaminergic neurons in animal models of Parkinson's disease. (C) 2009 Elsevier B.V. All rights reserved.