Abstract
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 56Fe, 12C, and 1H 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.
Highlights
Neuronal cells show great diversity in morphology and are highly organized within the animal brain [1]
Changes to cognition and other central nervous system (CNS) effects following charged particle exposures are of concern for medical patients undergoing radiation treatment in cancer therapy and for cosmic ray exposures to astronauts during space travel
Neuronal cell injury initiated by ionizing energy deposition involves a cascade of physico-chemical
Summary
Neuronal cells show great diversity in morphology and are highly organized within the animal brain [1]. Neuronal cells are dynamic, as branches may extend and immature filopodia seek new connections to make synapses with cellular cues [4,5]. The dentate gyrus (DG) in the hippocampus shows great similarity in cellular morphology and neurocircuitry across mammalian species [8]. The principal neurons in the dentate gyrus are dentate granule cells (DGCs) [9,10]. The DGC dendrites extend perpendicularly to the granule cell layer, into the overlying molecular layer where they receive synaptic connections mainly from the entorhinal cortex via the perforant pathway. Mossy fibers are the axons of the granule cells extending from the basal level and making synapses with the pyramidal cells of CA3 region of the hippocampus [11,12]
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