Page 198 - 2014 Printable Abstract Book
P. 198
centrosomes following radiation exposure. These studies will aid in determining how age, radiation
quality, and tissue type impact the induction of radiation damage, an endpoint that has been associated
with the carcinogenic process.
(PS3-14) Cognitive impairment and dendritic alterations caused by low dose heavy-ion irradiation.
Barrett D. Allen; Vipan K. Parihar, PhD; Katherine Tran; Nicole N. Chmielewski; Brianna M. Craver; and
Charles L. Limoli, University of California, Irvine, Irvine, CA
Ejection events from the solar particles and galactic cosmic rays pose a unique hazard for
astronauts because they contain charged particles that can damage cells and tissues as they traverse the
body. Evidence suggests that radiation exposure is particularly deleterious to the brain, where alterations
to the complex neuronal structure may compromise function and hasten neurodegeneration. We
hypothesize that exposure to low dose charged particle irradiation would elicit ultrastructural changes in
neuronal architecture, alterations in dendritic spine density and synaptic plasticity that would be
contributory if not causal to cognitive impairments. To determine this, we irradiated 6-month old Thy1-
EGFP transgenic mice with oxygen or titanium (5 or 30 cGy) ions (600 MeV). At 12 weeks post irradiation,
mice were tested for novel object recognition, preference for novel place and temporal order-dependent
memory using a series of open arena tests. Our data reveals that exposure to titanium ions impaired
object and place recognition memory, where the tendency to explore novel object or place was reduced
significantly (P<0.05) in irradiated versus non-irradiated mice. Furthermore, performance on the temporal
order test was significantly impaired (P<0.05) compared to controls. Interestingly, mice exposed to oxygen
particles showed no cognitive impairments and preferred novel and familiar object or place equally during
the testing phase. Analysis of dendritic complexity in neurons of the granule cell layer (GCL) showed a
dose dependent reduction in dendritic length (20 to 28%), branching (15 %) and dendritic volume (25%)
after exposure to titanium ions. Furthermore, immunohistochemical analysis of granule cell neurons in
the dentate gyrus of mice exposed to oxygen or titanium revealed significant elevations in postsynaptic
density protein (PSD-95) compared to non-irradiated mice. These findings demonstrate for the first time,
persistent and dose-responsive changes in dendritic complexity, synaptic protein levels and cognitive
decrements following exposure to charged particle irradiation. [Supported by: NASA Grants NNX13AD59G
and NNX10AD59G, C.L.L.].
(PS3-15) Sustained TNF-α positive feedback loop in response to radiation exposure potentiates pro-
2
1
tumorigenic to pre-malignant phenotype. Krishnan Manickam, PhD ; Natarajan Aravindan, PhD ;
3
1
1
1
Sumathy Mohan, PhD ; Colleen Gaudette, BS ; Preethi Janardhanan, MS ; Eleanor Blakely, PhD ; and
1
1
Mohan Natarajan, PhD ; Department of Pathology, UT Health Science Center, San Antonio, TX ;
2
Department of Radiation Oncology, University of Oklahoma Health Sciences Center, Oklahoma, OK ; and
Life Sciences Division, LBNL, Berkeley, CA
3
The goal of this study is to understand whether sustained amplification of the NF-kB-TNF-α
positive feedback loop has any influence on stimulation of predisposing factors for radiation-induced
carcinogenesis, and/or potentiates pro-tumorigenic cells to the pre-malignant phenotype. Breast pro-
56
tumorigenic cells, MCF-10A were exposed to high-LET heavy ion ( Fe; 600 MeV/amu) radiation at a total
dose of 0.8 or 1.6 Gy and at a dose rate of 1 Gy/min. Cells cultured at similar conditions and exposed to
196 | P a g e
quality, and tissue type impact the induction of radiation damage, an endpoint that has been associated
with the carcinogenic process.
(PS3-14) Cognitive impairment and dendritic alterations caused by low dose heavy-ion irradiation.
Barrett D. Allen; Vipan K. Parihar, PhD; Katherine Tran; Nicole N. Chmielewski; Brianna M. Craver; and
Charles L. Limoli, University of California, Irvine, Irvine, CA
Ejection events from the solar particles and galactic cosmic rays pose a unique hazard for
astronauts because they contain charged particles that can damage cells and tissues as they traverse the
body. Evidence suggests that radiation exposure is particularly deleterious to the brain, where alterations
to the complex neuronal structure may compromise function and hasten neurodegeneration. We
hypothesize that exposure to low dose charged particle irradiation would elicit ultrastructural changes in
neuronal architecture, alterations in dendritic spine density and synaptic plasticity that would be
contributory if not causal to cognitive impairments. To determine this, we irradiated 6-month old Thy1-
EGFP transgenic mice with oxygen or titanium (5 or 30 cGy) ions (600 MeV). At 12 weeks post irradiation,
mice were tested for novel object recognition, preference for novel place and temporal order-dependent
memory using a series of open arena tests. Our data reveals that exposure to titanium ions impaired
object and place recognition memory, where the tendency to explore novel object or place was reduced
significantly (P<0.05) in irradiated versus non-irradiated mice. Furthermore, performance on the temporal
order test was significantly impaired (P<0.05) compared to controls. Interestingly, mice exposed to oxygen
particles showed no cognitive impairments and preferred novel and familiar object or place equally during
the testing phase. Analysis of dendritic complexity in neurons of the granule cell layer (GCL) showed a
dose dependent reduction in dendritic length (20 to 28%), branching (15 %) and dendritic volume (25%)
after exposure to titanium ions. Furthermore, immunohistochemical analysis of granule cell neurons in
the dentate gyrus of mice exposed to oxygen or titanium revealed significant elevations in postsynaptic
density protein (PSD-95) compared to non-irradiated mice. These findings demonstrate for the first time,
persistent and dose-responsive changes in dendritic complexity, synaptic protein levels and cognitive
decrements following exposure to charged particle irradiation. [Supported by: NASA Grants NNX13AD59G
and NNX10AD59G, C.L.L.].
(PS3-15) Sustained TNF-α positive feedback loop in response to radiation exposure potentiates pro-
2
1
tumorigenic to pre-malignant phenotype. Krishnan Manickam, PhD ; Natarajan Aravindan, PhD ;
3
1
1
1
Sumathy Mohan, PhD ; Colleen Gaudette, BS ; Preethi Janardhanan, MS ; Eleanor Blakely, PhD ; and
1
1
Mohan Natarajan, PhD ; Department of Pathology, UT Health Science Center, San Antonio, TX ;
2
Department of Radiation Oncology, University of Oklahoma Health Sciences Center, Oklahoma, OK ; and
Life Sciences Division, LBNL, Berkeley, CA
3
The goal of this study is to understand whether sustained amplification of the NF-kB-TNF-α
positive feedback loop has any influence on stimulation of predisposing factors for radiation-induced
carcinogenesis, and/or potentiates pro-tumorigenic cells to the pre-malignant phenotype. Breast pro-
56
tumorigenic cells, MCF-10A were exposed to high-LET heavy ion ( Fe; 600 MeV/amu) radiation at a total
dose of 0.8 or 1.6 Gy and at a dose rate of 1 Gy/min. Cells cultured at similar conditions and exposed to
196 | P a g e
