Imaging multiple phases of neurodegeneration: a novel approach to assessing cell death in vivo.
Imaging multiple phases of neurodegeneration: a novel approach to assessing cell death in vivo.
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DOI：
10.1038/cddis.2009.3
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发表时间：
2010
影响因子：
9
通讯作者：
中科院分区：
文献类型：
--
作者：
神经细胞死亡是所有神经退行性疾病中的关键事件，细胞凋亡和坏死是急性和慢性退行性过程的中心。然而，到目前为止，还不可能动态地和真实的时间地研究这些。在这项研究中，我们使用光谱上不同的，公认的荧光细胞死亡标志物，使时间分辨率和定量的早期和晚期阶段的细胞凋亡和坏死的单个神经细胞在不同的疾病模型。在同一只活体眼睛中追踪数小时、数天、数周和数月的单细胞死亡概况是目前可用技术的重大进步。我们确定了慢性模型中晚期凋亡细胞与早期凋亡细胞的数量优势，加强了不同疾病模型中细胞机制之间的共性。我们表明，MK 801有效地抑制细胞凋亡和坏死，但我们的研究结果支持使用我们的技术来研究具有明确靶点的更特异性的抗细胞凋亡和抗坏死策略，具有更大的临床应用潜力。眼睛的光学特性为定量监测实验性神经变性的疾病机制和动力学提供了令人信服的机会。我们的研究结果还有助于直接观察患者的视网膜神经细胞死亡，作为改进诊断，跟踪疾病状态和评估治疗干预的辅助手段。
Nerve cell death is the key event in all neurodegenerative disorders, with apoptosis and necrosis being central to both acute and chronic degenerative processes. However, until now, it has not been possible to study these dynamically and in real time. In this study, we use spectrally distinct, well-recognised fluorescent cell death markers to enable the temporal resolution and quantification of the early and late phases of apoptosis and necrosis of single nerve cells in different disease models. The tracking of single-cell death profiles in the same living eye over hours, days, weeks and months is a significant advancement on currently available techniques. We identified a numerical preponderance of late-phase versus early-phase apoptotic cells in chronic models, reinforcing the commonalities between cellular mechanisms in different disease models. We showed that MK801 effectively inhibited both apoptosis and necrosis, but our findings support the use of our technique to investigate more specific anti-apoptotic and anti-necrotic strategies with well-defined targets, with potentially greater clinical application. The optical properties of the eye provide compelling opportunities for the quantitative monitoring of disease mechanisms and dynamics in experimental neurodegeneration. Our findings also help to directly observe retinal nerve cell death in patients as an adjunct to refining diagnosis, tracking disease status and assessing therapeutic intervention.
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影响因子：
5.3
作者：
Li, Q;Lau, A;Stanley, EF
通讯作者：
Stanley, EF
影响因子：
5.3
作者：
Cellerino, A;Galli- Resta, L;Colombaioni, L
通讯作者：
Colombaioni, L
影响因子：
4.2
作者：
Cheung, ZH;So, KF;Chen, CF
通讯作者：
Chen, CF
影响因子：
3.7
作者：
Kvam E;Nannenga BL;Wang MS;Jia Z;Sierks MR;Messer A
通讯作者：
Messer A
影响因子：
2.9
作者：
Miguel-Hidalgo, JJ;Alvarez, XA;Quack, G
通讯作者：
Quack, G