Chemotherapy has been successfully used to reduce radiation dose and volume for most pediatric patients. However, because of the failure of chemotherapeutic agents to cross the blood-brain barrier and the lack of response of some brain tumors to these agents, radiation therapy is still used to treat many childhood cancers with CNS involvement. In this study, we investigated the radiation effects on cognition and dendritic structure in the hippocampus in juvenile male mice. Twenty-one-day-old male C57BL/6 mice were irradiated using the small animal radiation research platform (SARRP). Animals were exposed to either a 10 Gy single dose or 10 Gy × 2 fractionated doses of X-ray cranial radiation. Five weeks after irradiation, animals were tested for hippocampus-dependent cognitive performance in the Morris water maze. Significant impairment in spatial memory retention was observed in the probe trial after the first day of hidden-platform training (first probe trial) in animals that received either 10 Gy single-dose or 10 Gy × 2 fractionated doses. However, by day 5, mice that received a 10 Gy single dose showed spatial memory retention in the probe trials, whereas mice that received the 20 Gy fractionated doses remained impaired. During Y-maze testing, animals exposed to radiation were impaired; the irradiated mice were not able to distinguish among the three Y-maze arms and spent approximately the same amount of time in all three arms during the retention trial. Radiation significantly compromised the dendritic architecture and reduced spine density throughout the hippocampal trisynaptic network.
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1 June 2018
REGULAR ARTICLES|
March 27 2018
Behavioral Effects of Focal Irradiation in a Juvenile Murine Model
Tyler C. Alexander;
Tyler C. Alexander
aDivision of Radiation Health, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205
bDepartment of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205
Scholars-in-Training, Radiation Research Society.
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Hannah Butcher;
Hannah Butcher
aDivision of Radiation Health, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205
bDepartment of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205
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Kimberly Krager;
Kimberly Krager
aDivision of Radiation Health, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205
bDepartment of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205
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Frederico Kiffer;
Frederico Kiffer
aDivision of Radiation Health, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205
bDepartment of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205
Scholars-in-Training, Radiation Research Society.
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Thomas Groves;
Thomas Groves
aDivision of Radiation Health, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205
bDepartment of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205
cDepartment of Neurobiology & Developmental Sciences, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205
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Jing Wang;
Jing Wang
aDivision of Radiation Health, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205
bDepartment of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205
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Gwendolyn Carter;
Gwendolyn Carter
aDivision of Radiation Health, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205
bDepartment of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205
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Antiño R. Allen
Antiño R. Allen
2
aDivision of Radiation Health, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205
bDepartment of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205
cDepartment of Neurobiology & Developmental Sciences, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205
2Address for correspondence: University of Arkansas for Medical Sciences, 4301 W. Markham, 441B-2, Little Rock, AR 72205; email: AAllen@uams.edu.
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Radiat Res (2018) 189 (6): 605–617.
Article history
Received:
May 30 2017
Accepted:
February 20 2018
Citation
Tyler C. Alexander, Hannah Butcher, Kimberly Krager, Frederico Kiffer, Thomas Groves, Jing Wang, Gwendolyn Carter, Antiño R. Allen; Behavioral Effects of Focal Irradiation in a Juvenile Murine Model. Radiat Res 1 June 2018; 189 (6): 605–617. doi: https://doi.org/10.1667/RR14847.1
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