Irradiation of Neurons with High-Energy Charged Particles: An In Silico Modeling Approach
Irradiation of Neurons with High-Energy Charged Particles: An In Silico Modeling Approach
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DOI：
10.1371/journal.pcbi.1004428
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发表时间：
2015-08-01
影响因子：
4.3
通讯作者：
Cucinotta, Francis A.
中科院分区：
文献类型：
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作者：
Alp, Murat;Parihar, Vipan K.;Cucinotta, Francis A.
在这项工作中，首次使用微观能量沉积事件的随机计算模型来研究辐照对小鼠海马神经元细胞的损伤。为不同粒子类型创建了一个广泛的辐射轨迹库，以记录能量沉积在描述神经元形态的小体素和体积段中，随后对给定的粒子影响或剂量进行采样。方法采用神经形态网（neuromorpho.org）构建小鼠海马颗粒细胞，沿树突分支随机分布脊椎和丝状足节段。该模型用高能Fe-56、C-12和H-1粒子和电子进行了测试。结果表明，在评估细胞损伤时，神经元形态的树形结构和不同颗粒的微观剂量沉积可能导致不同的结果，导致相同吸收剂量下结构损伤的差异。微观剂量在神经元成分中的意义在于引入特定的局部和全局细胞损伤模式，这些细胞损伤可能导致脊柱、丝状足和树突修剪，影响认知，并可能导致神经元崩溃。结果表明，与电子的均匀剂量分布相比，低剂量下重粒子轨迹的不均匀性以及神经元形态的不均匀性使得有必要对特定神经元成分的空间剂量描绘进行建模。展望未来，这项工作可以通过在纳米尺度上准确描述复杂神经元结构的潜在物理损伤，直接支持低剂量带电粒子照射后观察到的脊柱和树突形态改变的生物物理模型的发展。
In this work, a stochastic computational model of microscopic energy deposition events is used to study for the first time damage to irradiated neuronal cells of the mouse hippocampus. An extensive library of radiation tracks for different particle types is created to score energy deposition in small voxels and volume segments describing a neuron's morphology that later are sampled for given particle fluence or dose. Methods included the construction of in silico mouse hippocampal granule cells from neuromorpho.org with spine and filopodia segments stochastically distributed along the dendritic branches. The model is tested with high-energy Fe-56, C-12, and H-1 particles and electrons. Results indicate that the tree-like structure of the neuronal morphology and the microscopic dose deposition of distinct particles may lead to different outcomes when cellular injury is assessed, leading to differences in structural damage for the same absorbed dose. The significance of the microscopic dose in neuron components is to introduce specific local and global modes of cellular injury that likely contribute to spine, filopodia, and dendrite pruning, impacting cognition and possibly the collapse of the neuron. Results show that the heterogeneity of heavy particle tracks at low doses, compared to the more uniform dose distribution of electrons, juxtaposed with neuron morphology make it necessary to model the spatial dose painting for specific neuronal components. Going forward, this work can directly support the development of biophysical models of the modifications of spine and dendritic morphology observed after low dose charged particle irradiation by providing accurate descriptions of the underlying physical insults to complex neuron structures at the nano-meter scale.