In vivo imaging of axonal transport using MRI: aging and Alzheimer's disease

In vivo imaging of axonal transport using MRI: aging and Alzheimer's disease
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DOI:
10.1007/s00259-007-0707-8
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发表时间:
2008-03-01
影响因子:
9.1
通讯作者:
Cross, Donna
Cross, Donna
中科院分区:
医学1区
文献类型:
--
作者:
Minoshima, Satoshi;Cross, Donna

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目的利用锰作为跨突触轴突示踪剂的MRI可以揭示活体轴突运输的动力学过程。我们使用这项技术来检验轴突运输受损是否是衰老和早期阿尔茨海默病(AD)的一个重要的病理生理过程,并在一定程度上解释了AD中投射神经元的“选择性易损性”。我们开发了基于体素的统计标测技术和基于质量传输的示踪剂动力学建模方法,用于评估衰老大鼠和AD转基因小鼠的轴突传输速率。结果这些技术显示,在衰老和AD动物模型中,锰增强了嗅束轴突投射的信号变化,降低了轴突传输速率。结论轴突传输的改变可能是衰老和AD的关键病理生理过程。锰增强MRI为AD和相关疾病轴突运输改变的研究提供了令人兴奋的机会。
Purpose MRI using manganese as a trans-synaptic axonal tracing agent can unveil dynamics of axonal transport in living subjects. We use this technology to test the hypotheses if impaired axonal transport is a significant pathophysiological process in aging and early Alzheimer's disease (AD) and in part accounting for "selective vulnerability" of projection neurons in AD.Methods To allow quantitative assessment of axonal transport in vivo, we developed voxel-based statistical mapping technology as well as a tracer kinetic modeling method based on mass transport for manganese-enhanced MRI to estimate axonal transport rates in aging rats and AD transgenic mice.Results These techniques demonstrated manganese-enhanced signal changes in axonal projections of the olfactory tract and decreased axonal transport rates in rodent models of aging and AD.Conclusion Altered axonal transport may be a critical pathophysiological process in aging and AD. Manganese-enhanced MRI provides exciting opportunities for the investigations of altered axonal transport in AD and related disorders.