How Do Rat Cortical Cells Cultured with Aluminum Die: Necrosis or Apoptosis?
How Do Rat Cortical Cells Cultured with Aluminum Die: Necrosis or Apoptosis?
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DOI：
10.1177/039463200802100112
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发表时间：
2008-01
影响因子：
3.5
通讯作者：
Qinli Zhang;P. Boscolo;P. Niu;Fang Wang;Ying-tao Shi;Ling Zhang;Lin-ping Wang;Jing Wang
中科院分区：
文献类型：
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作者：
Qinli Zhang;P. Boscolo;P. Niu;Fang Wang;Ying-tao Shi;Ling Zhang;Lin-ping Wang;Jing Wang
铝(Al)暴露被认为是几种神经退行性疾病中神经细胞丢失的原因。因此，明确铝中毒和退行性疾病中神经细胞死亡的机制可能有助于开发促进神经细胞存活的治疗药物。此外，对细胞死亡途径的了解可能有助于发现神经退行性变的治疗方法。然而，铝引发的神经细胞死亡模式还没有完全建立起来。本研究旨在了解铝诱导培养的大脑皮层细胞死亡的途径。取新生大鼠原代神经元、星形胶质细胞单独培养以及神经元/星形胶质细胞共培养，分别加入0、0.5、1.0、2.0 mM铝72h，用倒置显微镜、荧光显微镜和电子显微镜观察细胞形态的变化。同时用流式细胞仪检测细胞凋亡率。铝处理组神经元出现细胞皱缩、染色质聚集和碎裂、膜芽、膜结合的凋亡小体形成等形态特征，而铝处理组星形胶质细胞则未见上述特征。流式细胞仪检测凋亡率的定量结果显示，不同剂量的神经细胞呈现典型的凋亡进程。铝浓度与细胞凋亡率之间的浓度依赖关系证实，即使铝浓度低于2 mM，细胞凋亡也是原代培养神经元死亡的主要原因。在神经元/星形胶质细胞共培养中，有明显的坏死和凋亡，但与神经元相比，凋亡的强度要小得多，这表明星形胶质细胞可能对神经元在铝存在下的生存特别重要。
Aluminum (Al) exposure has been implicated as the cause of neural cells loss in several neurodegenerative diseases. Therefore, defining the mechanism of neural cell death in Al toxicity and degenerative diseases might lead to the development of therapeutic agents which promote neural cell survival. Furthermore, knowledge of cell death pathways might facilitate the discovery of treatments for neurodegeneration. However, the death mode of neural cells triggered by Al has not been firmly established. The present study focuses on understanding the pathway of cells death in cultured cortical cells treated with Al. Primary neurons cultured alone, astrocytes cultured alone, and neuron/astrocyte co-cultures obtained from newborn rats were incubated with Al at the concentrations of 0, 0.5,1.0, or 2.0 mM for 72 h. Morphological changes were observed with an inverted phase microscope, a fluorescent microscope, and an electron microscope. Simultaneously, the rate of apoptosis was quantified with flow cytometry. Morphological characteristics of apoptosis such as cell shrinkage, aggregation and fragmentation of chromatin, membrane buds, and formation of membrane-bound apoptotic bodies were observed in Al-treated neurons, while none of these characteristics were found in Al-treated astrocytes. Quantitative results of apoptotic rates detected with flow cytometry indicated a typical apoptosis progression in neurons at various dosages. A concentration-dependent relationship between Al concentration and apoptotic rates confirmed that apoptosis is the prominent cause of cell death in primary cultured neurons, even at a concentration lower than 2 mM. Both necrosis and apoptosis are evident in neuron/astrocyte co-cultures, but the intensity of apoptosis is much less compared with that of neurons, suggesting that astrocytes may be especially important for neuronal survival in the presence of Al.