Page 27 - 2014 Printable Abstract Book
P. 27
(Pres 103) In silico models of energy deposition by energetic particles in mouse hippocampus including
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neurons, dendritic trees and spines. Murat Alp ; Charles Limoli ; and Francis A. Cucinotta, University of
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2
Nevada, Las Vegas, Las Vegas, NV and University of California, Irvine, CA
Animal studies on the effects of low LET radiation including photons and protons, and high charge
and energy (HZE) radiation on brain structures have provided both detailed images of the neuronal
subsets and their quantified structural changes in time due to radiation damage. In this work the large
scale computational modeling studies on the effects of various radiation types including photons, protons
and HZE particle on the CNS can be methodically studied by unifying in-silico models of brain structures
and Monte Carlo simulation of particle track structure at the nanometer scale. In this study we employed
extensive neuroanatomical information of digital libraries of morphological data for mouse neuronal cells.
The hippocampus is composed of different but interconnected subdivisions of neuronal cell layers that
are identified structurally and functionally. Our in silico model of brain structures utilizes quantified
anatomical data on different classes of cell types including location, shape, volume, density as well as
the wiring diagrams of soma, dendrites, and spines in order to create ensembles of the structure.
Topological changes within the given structure can be also be considered.
We will first present our efforts on creating in silico models of granule cell layers in the dentate gyrus of
mouse hippocampus using scaling approaches to whole hippocampal cell types supported by available
neuro morphological data and theoretical studies. Our presentation of in silico models provides visual and
conceptual insight into the interaction of radiation particle tracks with neural morphology. We then
consider structural changes due to microscopic energy deposition integrating results from experimental
studies and thereby acquire model parameters of radiation damage in the modeled neuronal system.
A combined approach of experimental data and in silico models of CNS structures can lead to pre-dictions
on outcomes of therapeutic radiation and deleterious effect of space radiation in humans. Similarities in
hippocampal structure persists between the species, and our in silico approach can lead to predictions for
other species including humans. Simulation tools of neuronal electrical activity can also be included in in
silico models to bridge the gap between the structural damage and its functional manifestation in
electrophysiological measurements.
(Pres 104) Central nervous system responses to low doses of high LET radiation. Gregory A. Nelson, PhD,
Department of Basic Sciences, Division of Radiation Research, Loma Linda University, Loma Linda, CA
Potential health risks from exposure to charged particle radiation fields with compositions and
doses comparable to spaceflight operations include acute and late effects to the central nervous system
(CNS). There is concern that radiation exposure may alter network function, disturb cognitive function,
and accelerate the pathogenesis of late degenerative diseases. It has long been appreciated that high
doses of radiation to the brain can result in tissue degeneration including demyelination and vascular
defects. Effects at doses less than ~2 Gy or following charged particle exposure are less well characterized
but are not associated with gross tissue destruction. In the CNS, heavy ion radiation blocks neurogenesis
in the hippocampus and alters the differentiation of neural precursor cells; this may impair cognitive
functions such as spatial memory. Persistent neuroinflammation and oxidative stress accompany CNS
irradiation and contribute to changes in structure and function. Electrophysiological changes include
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2
1
1
neurons, dendritic trees and spines. Murat Alp ; Charles Limoli ; and Francis A. Cucinotta, University of
1
2
Nevada, Las Vegas, Las Vegas, NV and University of California, Irvine, CA
Animal studies on the effects of low LET radiation including photons and protons, and high charge
and energy (HZE) radiation on brain structures have provided both detailed images of the neuronal
subsets and their quantified structural changes in time due to radiation damage. In this work the large
scale computational modeling studies on the effects of various radiation types including photons, protons
and HZE particle on the CNS can be methodically studied by unifying in-silico models of brain structures
and Monte Carlo simulation of particle track structure at the nanometer scale. In this study we employed
extensive neuroanatomical information of digital libraries of morphological data for mouse neuronal cells.
The hippocampus is composed of different but interconnected subdivisions of neuronal cell layers that
are identified structurally and functionally. Our in silico model of brain structures utilizes quantified
anatomical data on different classes of cell types including location, shape, volume, density as well as
the wiring diagrams of soma, dendrites, and spines in order to create ensembles of the structure.
Topological changes within the given structure can be also be considered.
We will first present our efforts on creating in silico models of granule cell layers in the dentate gyrus of
mouse hippocampus using scaling approaches to whole hippocampal cell types supported by available
neuro morphological data and theoretical studies. Our presentation of in silico models provides visual and
conceptual insight into the interaction of radiation particle tracks with neural morphology. We then
consider structural changes due to microscopic energy deposition integrating results from experimental
studies and thereby acquire model parameters of radiation damage in the modeled neuronal system.
A combined approach of experimental data and in silico models of CNS structures can lead to pre-dictions
on outcomes of therapeutic radiation and deleterious effect of space radiation in humans. Similarities in
hippocampal structure persists between the species, and our in silico approach can lead to predictions for
other species including humans. Simulation tools of neuronal electrical activity can also be included in in
silico models to bridge the gap between the structural damage and its functional manifestation in
electrophysiological measurements.
(Pres 104) Central nervous system responses to low doses of high LET radiation. Gregory A. Nelson, PhD,
Department of Basic Sciences, Division of Radiation Research, Loma Linda University, Loma Linda, CA
Potential health risks from exposure to charged particle radiation fields with compositions and
doses comparable to spaceflight operations include acute and late effects to the central nervous system
(CNS). There is concern that radiation exposure may alter network function, disturb cognitive function,
and accelerate the pathogenesis of late degenerative diseases. It has long been appreciated that high
doses of radiation to the brain can result in tissue degeneration including demyelination and vascular
defects. Effects at doses less than ~2 Gy or following charged particle exposure are less well characterized
but are not associated with gross tissue destruction. In the CNS, heavy ion radiation blocks neurogenesis
in the hippocampus and alters the differentiation of neural precursor cells; this may impair cognitive
functions such as spatial memory. Persistent neuroinflammation and oxidative stress accompany CNS
irradiation and contribute to changes in structure and function. Electrophysiological changes include
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