Hippocampal dysfunction during the chronic phase following a single exposure to cranial irradiation.
Ionizing radiation can significantly affect brain functioning in adults. The present study assessed depression-like behaviors in adult C57BL/6 mice using the tail suspension test (TST) at 30 and 90days following a single cranial exposure to γ-rays (0, 1, or 10Gy) to evaluate hippocampus-related behavioral dysfunction during the chronic phase following cranial irradiation. Additionally, hippocampal neurogenesis, inflammatory cytokines, inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), brain-derived neurotrophic factor (BDNF), and glial cell line-derived neurotrophic factor (GDNF) were analyzed. At 30 and 90days following irradiation with 10Gy, mice displayed significant depression-like behaviors. We observed a persistent decrease in the number of cells positive for doublecortin, an immunohistochemical marker for neurogenesis, in the hippocampus from 1 to 90days after irradiation with 10Gy. Changes in the mRNA expression of inflammatory cytokines, including interleukin (IL)-1β, tumor necrosis factor-α, IL-6, and interferon-γ, were not correlated with the decrease in hippocampal neurogenesis or the appearance of depression-like behavior during the chronic phase following irradiation. However, at 30 and 90days after irradiation with 10Gy, the number of microglia was significantly decreased compared with age-matched sham-irradiated controls. The reduction in the chronic phase was consistent with the significant down-regulation in the mRNA expression of iNOS, COX-2, BDNF, and GDNF in the hippocampus. Therefore, hippocampal dysfunction during the chronic phase following cranial irradiation may be associated with decreases in the neurogenesis- and synaptic plasticity-related signals, concomitant with microglial reduction in the hippocampus.
College of Veterinary Medicine and Animal Medical Institute, Chonnam National University, Gwangju 500-757, South Korea.
Yeonghoon
Y
Son
College of Veterinary Medicine and Animal Medical Institute, Chonnam National University, Gwangju 500-757, South Korea; Department of Physiology and Neuroscience Program, Michigan State University, MI 48824, USA.
Miyoung
M
Yang
Research Center, Dongnam Institute of Radiological & Medical Sciences (DIRAMS), Busan 619-953, South Korea.
Joong-Sun
JS
Kim
College of Veterinary Medicine and Animal Medical Institute, Chonnam National University, Gwangju 500-757, South Korea.
Juhwan
J
Kim
College of Veterinary Medicine and Animal Medical Institute, Chonnam National University, Gwangju 500-757, South Korea.
Sung-Ho
SH
Kim
College of Veterinary Medicine and Animal Medical Institute, Chonnam National University, Gwangju 500-757, South Korea.
Jong-Choon
JC
Kim
Department of Veterinary Anatomy, College of Veterinary Medicine, Jeju National University, Jeju 690-756, South Korea.
Taekyun
T
Shin
Department of Physiology and Neuroscience Program, Michigan State University, MI 48824, USA.
Hongbing
H
Wang
Radiation Research Division for Bio-Technology Institute, Jeongeup Campus of Korea Atomic Energy Research Institute, Jeonbuk 580-185, South Korea.
Sung-Kee
SK
Jo
Radiation Research Division for Bio-Technology Institute, Jeongeup Campus of Korea Atomic Energy Research Institute, Jeonbuk 580-185, South Korea.
Uhee
U
Jung
College of Veterinary Medicine and Animal Medical Institute, Chonnam National University, Gwangju 500-757, South Korea. Electronic address: moonc@chonnam.ac.kr.
Changjong
C
Moon
D000818:Animals; D001927:Brain Diseases / Q000209:etiology / Q000503:physiopathology*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D003863:Depression / Q000209:etiology / Q000503:physiopathology; D015536:Down-Regulation / Q000235:genetics / Q000528:radiation effects; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000503:physiopathology* / Q000528:radiation effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000502:physiology / Q000528:radiation effects; D055495:Neurogenesis / Q000502:physiology / Q000528:radiation effects*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011832:Radiation Injuries / Q000150:complications / Q000503:physiopathology*; D011839:Radiation, Ionizing
D019208:Brain-Derived Neurotrophic Factor; D016207:Cytokines; D051100:Glial Cell Line-Derived Neurotrophic Factor; D012333:RNA, Messenger; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2
Depression-like behavior; Hippocampus; Ionizing radiation; Microglia; Neurogenesis; Neurotrophic factor