Page 270 - 2014 Printable Abstract Book
P. 270
(PS4-59) Contrasting the effects of proton irradiation on dendritic complexity of subiculum neurons in
WT and mCAT mice. Nicole N. Chmielewski; Vipan K. Parihar; and Charles L. Limoli, PhD, University of
California, Irvine, Irvine, CA
Exposure of the central nervous system (CNS) to ionizing radiation elicits varying degrees of
normal tissue damage that carries the risk of impairing cognitive function. Growing evidence has found
that radiation-induced oxidative stress directly effects a wide range of biological endpoints with an overall
negative impact on CNS function. We have recently published that mice over-expressing mitochondrial
human catalase (mCAT transgene) exhibit improved neurogenesis before and after proton irradiation,
suggesting a potential neuroprotective role in reducing mitochondrial oxidative stress. To further our
understanding of the potential neuroprotective properties of the mCAT transgene, we chose to look at
the subiculum, the hippocampal region that mediates the outward flow of information to the rest of the
CNS. Although understudied, the subiculum is associated with a broad spectrum of neurocognitive
functions, including receiving and relaying responses of fear, stress, anxiety, and memory formation in the
CNS. To test the impact of proton irradiation on the subiculum, 2-month-old WT and mCAT mice were
exposed 0.5 or 2 Gy whole body proton radiation (250 MeV). 1 month following irradiation subiculum
neurons were analyzed on a range of micromorphometric parameters. In morphometric quantification,
Golgi stained neurons were examined using the Neurolucida neuron tracing system (Microbrightfield) at
100x magnification. Un-irradiated samples showed more robust dendritic complexity in mCAT compared
to WT strains. However, proton exposure significantly reduced dendritic complexity of subiculum neurons
in a dose dependent manner in both WT and mCAT strains. Reductions in dendritic branching (20 to 50%),
length (20 to 40%), and area (30 to 60%) suggests that the mCAT transgene was unable to preserve
morphology in the subiculum following irradiation. Quantification of dendritic spines revealed that both
WT and mCAT mice had dose dependent reductions in the number (15 to 20%) and density (30 to 40%) of
spines. Although mCAT may ameliorate the oxidative responses after irradiation in other regions of the
brain, this data suggests that the over-expression of human catalase in the mitochondria does not
attenuate radiation-induced alterations in subiculum neurons.
1
1
(PS4-61) Radiation associated tumor oxygen dynamics. Michael W. Kissick, PhD ; Erin Adamson ; David
1
1
1
1
1
1
2
Campos ; Kevin Eliceiri ; Sean Fain ; Leonard Che Fru ; Steven Jacques ; Albert van der Kogel ; David Niles ;
1
1
1
Alexandra Torres ; and Randall Kimple, University of Wisconsin - Madison, Madison, WI and Oregon
2
Health and Science University, Portland, OR
Adaptive and hypofractionated radiotherapy could benefit from knowledge of the changing local
tumor oxygen concentrations over a variety of time scales. To guide such treatments, a diffuse optical
probe system was developed to spatially average the oxygen tension in xenografts of human head and
neck cancers transplanted into nude mice. The blood volume and hemoglobin saturation were measured
in real time. The quantities were measured with spectral fitting before and after irradiation with a dose
of 10 Gy of X-rays. An MRI BOLD scan was acquired before and after irradiation that measured regional
changes in R2* which is inversely proportional to oxygen availability. The mean fluorescent lifetime of
bound versus unbound NADH was measured before and after 10 Gy in human head and neck cancer cell
lines in vitro, in comparison with a control treatment of potassium cyanide (KCN). Simulations were
performed to fit the blood oxygen dynamics and infer changes in hypoxia within the tumor. The results of
these experiments are as follows: 1. the optical probe measured nearly constant blood volume and a
268 | P a g e
WT and mCAT mice. Nicole N. Chmielewski; Vipan K. Parihar; and Charles L. Limoli, PhD, University of
California, Irvine, Irvine, CA
Exposure of the central nervous system (CNS) to ionizing radiation elicits varying degrees of
normal tissue damage that carries the risk of impairing cognitive function. Growing evidence has found
that radiation-induced oxidative stress directly effects a wide range of biological endpoints with an overall
negative impact on CNS function. We have recently published that mice over-expressing mitochondrial
human catalase (mCAT transgene) exhibit improved neurogenesis before and after proton irradiation,
suggesting a potential neuroprotective role in reducing mitochondrial oxidative stress. To further our
understanding of the potential neuroprotective properties of the mCAT transgene, we chose to look at
the subiculum, the hippocampal region that mediates the outward flow of information to the rest of the
CNS. Although understudied, the subiculum is associated with a broad spectrum of neurocognitive
functions, including receiving and relaying responses of fear, stress, anxiety, and memory formation in the
CNS. To test the impact of proton irradiation on the subiculum, 2-month-old WT and mCAT mice were
exposed 0.5 or 2 Gy whole body proton radiation (250 MeV). 1 month following irradiation subiculum
neurons were analyzed on a range of micromorphometric parameters. In morphometric quantification,
Golgi stained neurons were examined using the Neurolucida neuron tracing system (Microbrightfield) at
100x magnification. Un-irradiated samples showed more robust dendritic complexity in mCAT compared
to WT strains. However, proton exposure significantly reduced dendritic complexity of subiculum neurons
in a dose dependent manner in both WT and mCAT strains. Reductions in dendritic branching (20 to 50%),
length (20 to 40%), and area (30 to 60%) suggests that the mCAT transgene was unable to preserve
morphology in the subiculum following irradiation. Quantification of dendritic spines revealed that both
WT and mCAT mice had dose dependent reductions in the number (15 to 20%) and density (30 to 40%) of
spines. Although mCAT may ameliorate the oxidative responses after irradiation in other regions of the
brain, this data suggests that the over-expression of human catalase in the mitochondria does not
attenuate radiation-induced alterations in subiculum neurons.
1
1
(PS4-61) Radiation associated tumor oxygen dynamics. Michael W. Kissick, PhD ; Erin Adamson ; David
1
1
1
1
1
1
2
Campos ; Kevin Eliceiri ; Sean Fain ; Leonard Che Fru ; Steven Jacques ; Albert van der Kogel ; David Niles ;
1
1
1
Alexandra Torres ; and Randall Kimple, University of Wisconsin - Madison, Madison, WI and Oregon
2
Health and Science University, Portland, OR
Adaptive and hypofractionated radiotherapy could benefit from knowledge of the changing local
tumor oxygen concentrations over a variety of time scales. To guide such treatments, a diffuse optical
probe system was developed to spatially average the oxygen tension in xenografts of human head and
neck cancers transplanted into nude mice. The blood volume and hemoglobin saturation were measured
in real time. The quantities were measured with spectral fitting before and after irradiation with a dose
of 10 Gy of X-rays. An MRI BOLD scan was acquired before and after irradiation that measured regional
changes in R2* which is inversely proportional to oxygen availability. The mean fluorescent lifetime of
bound versus unbound NADH was measured before and after 10 Gy in human head and neck cancer cell
lines in vitro, in comparison with a control treatment of potassium cyanide (KCN). Simulations were
performed to fit the blood oxygen dynamics and infer changes in hypoxia within the tumor. The results of
these experiments are as follows: 1. the optical probe measured nearly constant blood volume and a
268 | P a g e
