Biophysics Model of Heavy-Ion Degradation of Neuron Morphology in Mouse Hippocampal Granular Cell Layer Neurons.
Biophysics Model of Heavy-Ion Degradation of Neuron Morphology in Mouse Hippocampal Granular Cell Layer Neurons.
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DOI：
10.1667/rr14923.1
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发表时间：
2018-03
影响因子：
3.4
通讯作者：
Cucinotta FA
中科院分区：
文献类型：
--
作者：
Alp M;Cucinotta FA
在癌症治疗或太空旅行期间暴露于重离子辐射可能会导致与神经元形态和可塑性变化相关的认知障碍。在小鼠中观察到神经元树突复杂性降低，揭示了对辐射质量和吸收剂量的依赖性，这表明微观能量沉积起着重要作用。在这项工作中，我们使用小鼠齿状颗粒细胞层（GCL）神经元的形态学数据和随机模型的粒子轨道结构和微观能量沉积（艾德）开发的预测模型的高电荷和能量（HZE）粒子诱导的形态学变化的复杂结构的树突状乔木。我们将枝晶表示为具有单位纵横比的不同直径的圆柱段，并开发了一种快速采样方法来考虑重离子路径周围的δ射线（二次电子）的艾德随机分布，以减少计算时间。我们引入概率模型与少量的参数来描述诱导的前驱病变之前，树突状剪断，表示为剪断网站。考虑了LET分别为16.3和129 keV/μm的氧（16 O，600 MeV/n）和钛（48 Ti，600 MeV/n）粒子的预测。描述了用于量化神经元形态变化的形态测量参数，包括总树突长度、分支点数和分支数的减少。Sholl分析应用于单个神经元，以阐明树突复杂性的剂量依赖性降低。我们预测，由于神经元死亡通过索马细胞凋亡和过度的树突长度减少的作用，从脑切片的组织成像与单神经元细胞观察的测量值的重要差异。为了进一步阐明轨道结构的作用，随机片段切除（剪）模型和灵敏度研究的神经元死亡的模式在形态参数的预测的影响进行了说明。本研究的一个重要结论是，由于损伤部位的大空间分布，δ射线在神经元形态变化中起主要作用，这导致与局部损伤部位的艾德引起的损伤相比，对LET的依赖性降低，包括16 O和48 Ti之间的适度差异。
Exposure to heavy-ion radiation during cancer treatment or space travel may cause cognitive detriments that have been associated with changes in neuron morphology and plasticity. Observations in mice of reduced neuronal dendritic complexity have revealed a dependence on radiation quality and absorbed dose, suggesting that microscopic energy deposition plays an important role. In this work we used morphological data for mouse dentate granular cell layer (GCL) neurons and a stochastic model of particle track structure and microscopic energy deposition (ED) to develop a predictive model of high-charge and energy (HZE) particle-induced morphological changes to the complex structures of dendritic arbors. We represented dendrites as cylindrical segments of varying diameter with unit aspect ratios, and developed a fast sampling method to consider the stochastic distribution of ED by δ rays (secondary electrons) around the path of heavy ions, to reduce computational times. We introduce probabilistic models with a small number of parameters to describe the induction of precursor lesions that precede dendritic snipping, denoted as snip sites. Predictions for oxygen (16O, 600 MeV/n) and titanium (48Ti, 600 MeV/n) particles with LET of 16.3 and 129 keV/μm, respectively, are considered. Morphometric parameters to quantify changes in neuron morphology are described, including reduction in total dendritic length, number of branch points and branch numbers. Sholl analysis is applied for single neurons to elucidate dose-dependent reductions in dendritic complexity. We predict important differences in measurements from imaging of tissues from brain slices with single neuron cell observations due to the role of neuron death through both soma apoptosis and excessive dendritic length reduction. To further elucidate the role of track structure, random segment excision (snips) models are introduced and a sensitivity study of the effects of the modes of neuron death in predictions of morphometric parameters is described. An important conclusion of this study is that δ rays play a major role in neuron morphological changes due to the large spatial distribution of damage sites, which results in a reduced dependence on LET, including modest difference between 16O and 48Ti, compared to damages resulting from ED in localized damage sites.