Page 279 - 2014 Printable Abstract Book
P. 279
(PS4-75) HZE particle radiation enhances pattern separation - but diminishes hippocampal
1
2
1
1
neurogenesis - in adult mice. Melanie J. Lucero ; Rachel L. Redfield ; Naoki Ito ; Hung-Ying Shih ; Phillip
2
1
1
1
D. Rivera ; Shari G. Birnbaum ; Benjamin P.C. Chen ; Amelia J. Eisch, UT Southwestern Medical Center,
1
Dept. of Psychiatry, Dallas, TX and UT Southwestern Medical Center, Dept. of Radiation Oncology,
Dallas, TX
2
Astronauts on deep space missions will be exposed to chronic low doses of HZE (high-mass, high-
charged) radiation, which negatively influences the central nervous system, particularly the hippocampus.
This raises concerns that space radiation may diminish hippocampal function (e.g. by decreasing memory
or mood control), and thus compromise mission success. However, it is unknown how radiation alters
subtle aspects of hippocampal function, such as the ability of the hippocampus to distinguish specific
contexts, termed “pattern separation”, particularly in “astronaut-age” mature mice. To fill these
knowledge gaps, we exposed mice (9-week old Young Adult mice or ~6-month-old Mature mice) to HZE
particles (28Si, 275 MeV/n, 72.1 KeV/μm LET or 56Fe, 600 MeV/n, 174.1 KeV/μm LET) and examined
general behavior (e.g. locomotion) and hippocampal-dependent function (contextual fear conditioning,
CFC; contextual discrimination fear conditioning, CDFC) two to six months post-irradiation. For the 28Si
HZE particle radiation experiment, Young Adult and Mature mice received one of three treatments: a
single exposure of 20 cGy, a single exposure of 100 cGy, or 0 cGy (Sham). For the 56Fe HZE particle
experiment, mice received a single exposure of 20 cGy (Non-fractionated), a protracted dose of 20 cGy
(Fractionated, 6.7 cGy x 3 days, 48h intervals), or 0 cGy (Sham). After irradiation, Young Adult mice showed
normal general behavior, but diminished CFC and dose-dependent effects on CDFC. In contrast, mature
mice displayed normal locomotor activity and normal CFC. Interestingly, Mature irradiated mice showed
improved CDFC compared to Sham. Quantification of immature neuron number showed irradiation-
induced decrease in doublecortin immunoreactive hippocampal cells in both Young Adult and Mature
mice, showing that the improvement in CDFC in Mature mice was unexpectedly neurogenesis-
independent. These findings show that both 28Si and 56Fe HZE particle radiation enhances pattern
separation in older, fully mature mice, but have detrimental effects on hippocampal function in younger
mice. Ongoing work is currently exploring non-neurogenesis explanations for the age-related
improvement in pattern separation ability after exposure to HZE particles.
(PS4-77) Recovery of oligodendrocyte progenitor cells from fractionated and single dose irradiation.
Sage Begolly; John A. Olschowka; Jacqueline P. Williams; and M. Kerry O'Banion, University of Rochester,
Rochester, NY
Treatment of central nervous system (CNS) cancers and CNS metastases typically involves
fractionated irradiation (IR), with a current trend for high dose stereotactic approaches. While
fractionated IR regimens are designed to minimize the adverse effects to surrounding normal tissue seen
with single high dose IR, phenomena like the loss of myelin associated with radiation necrosis and
cognitive deficits still occur in patients undergoing CNS radiotherapy. Oligodendrocyte progenitor cells
(OPCs), which become the myelinating cells of the CNS, are mitotic throughout their lifespan and,
therefore, are a target for IR. Furthermore, the normal OPC cell cycle of 37 days has been shown to
decrease with some forms of trauma, suggesting that fractionated IR patterns may increase the damage
277 | P a g e
1
2
1
1
neurogenesis - in adult mice. Melanie J. Lucero ; Rachel L. Redfield ; Naoki Ito ; Hung-Ying Shih ; Phillip
2
1
1
1
D. Rivera ; Shari G. Birnbaum ; Benjamin P.C. Chen ; Amelia J. Eisch, UT Southwestern Medical Center,
1
Dept. of Psychiatry, Dallas, TX and UT Southwestern Medical Center, Dept. of Radiation Oncology,
Dallas, TX
2
Astronauts on deep space missions will be exposed to chronic low doses of HZE (high-mass, high-
charged) radiation, which negatively influences the central nervous system, particularly the hippocampus.
This raises concerns that space radiation may diminish hippocampal function (e.g. by decreasing memory
or mood control), and thus compromise mission success. However, it is unknown how radiation alters
subtle aspects of hippocampal function, such as the ability of the hippocampus to distinguish specific
contexts, termed “pattern separation”, particularly in “astronaut-age” mature mice. To fill these
knowledge gaps, we exposed mice (9-week old Young Adult mice or ~6-month-old Mature mice) to HZE
particles (28Si, 275 MeV/n, 72.1 KeV/μm LET or 56Fe, 600 MeV/n, 174.1 KeV/μm LET) and examined
general behavior (e.g. locomotion) and hippocampal-dependent function (contextual fear conditioning,
CFC; contextual discrimination fear conditioning, CDFC) two to six months post-irradiation. For the 28Si
HZE particle radiation experiment, Young Adult and Mature mice received one of three treatments: a
single exposure of 20 cGy, a single exposure of 100 cGy, or 0 cGy (Sham). For the 56Fe HZE particle
experiment, mice received a single exposure of 20 cGy (Non-fractionated), a protracted dose of 20 cGy
(Fractionated, 6.7 cGy x 3 days, 48h intervals), or 0 cGy (Sham). After irradiation, Young Adult mice showed
normal general behavior, but diminished CFC and dose-dependent effects on CDFC. In contrast, mature
mice displayed normal locomotor activity and normal CFC. Interestingly, Mature irradiated mice showed
improved CDFC compared to Sham. Quantification of immature neuron number showed irradiation-
induced decrease in doublecortin immunoreactive hippocampal cells in both Young Adult and Mature
mice, showing that the improvement in CDFC in Mature mice was unexpectedly neurogenesis-
independent. These findings show that both 28Si and 56Fe HZE particle radiation enhances pattern
separation in older, fully mature mice, but have detrimental effects on hippocampal function in younger
mice. Ongoing work is currently exploring non-neurogenesis explanations for the age-related
improvement in pattern separation ability after exposure to HZE particles.
(PS4-77) Recovery of oligodendrocyte progenitor cells from fractionated and single dose irradiation.
Sage Begolly; John A. Olschowka; Jacqueline P. Williams; and M. Kerry O'Banion, University of Rochester,
Rochester, NY
Treatment of central nervous system (CNS) cancers and CNS metastases typically involves
fractionated irradiation (IR), with a current trend for high dose stereotactic approaches. While
fractionated IR regimens are designed to minimize the adverse effects to surrounding normal tissue seen
with single high dose IR, phenomena like the loss of myelin associated with radiation necrosis and
cognitive deficits still occur in patients undergoing CNS radiotherapy. Oligodendrocyte progenitor cells
(OPCs), which become the myelinating cells of the CNS, are mitotic throughout their lifespan and,
therefore, are a target for IR. Furthermore, the normal OPC cell cycle of 37 days has been shown to
decrease with some forms of trauma, suggesting that fractionated IR patterns may increase the damage
277 | P a g e
