PMID- 24491956 OWN - NLM STAT- MEDLINE DCOM- 20140519 LR - 20140311 IS - 1090-2430 (Electronic) IS - 0014-4886 (Linking) VI - 254 DP - 2014 Apr TI - Hippocampal dysfunction during the chronic phase following a single exposure to cranial irradiation. PG - 134-44 LID - S0014-4886(14)00031-4 [pii] LID - 10.1016/j.expneurol.2014.01.018 [doi] AB - 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 gamma-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)-1beta, tumor necrosis factor-alpha, IL-6, and interferon-gamma, 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. CI - Copyright (c) 2014 Elsevier Inc. All rights reserved. FAU - Son, Yeonghoon AU - Son Y AD - College of Veterinary Medicine and Animal Medical Institute, Chonnam National University, Gwangju 500-757, South Korea. FAU - Yang, Miyoung AU - Yang M AD - 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. FAU - Kim, Joong-Sun AU - Kim JS AD - Research Center, Dongnam Institute of Radiological & Medical Sciences (DIRAMS), Busan 619-953, South Korea. FAU - Kim, Juhwan AU - Kim J AD - College of Veterinary Medicine and Animal Medical Institute, Chonnam National University, Gwangju 500-757, South Korea. FAU - Kim, Sung-Ho AU - Kim SH AD - College of Veterinary Medicine and Animal Medical Institute, Chonnam National University, Gwangju 500-757, South Korea. FAU - Kim, Jong-Choon AU - Kim JC AD - College of Veterinary Medicine and Animal Medical Institute, Chonnam National University, Gwangju 500-757, South Korea. FAU - Shin, Taekyun AU - Shin T AD - Department of Veterinary Anatomy, College of Veterinary Medicine, Jeju National University, Jeju 690-756, South Korea. FAU - Wang, Hongbing AU - Wang H AD - Department of Physiology and Neuroscience Program, Michigan State University, MI 48824, USA. FAU - Jo, Sung-Kee AU - Jo SK AD - Radiation Research Division for Bio-Technology Institute, Jeongeup Campus of Korea Atomic Energy Research Institute, Jeonbuk 580-185, South Korea. FAU - Jung, Uhee AU - Jung U AD - Radiation Research Division for Bio-Technology Institute, Jeongeup Campus of Korea Atomic Energy Research Institute, Jeonbuk 580-185, South Korea. FAU - Moon, Changjong AU - Moon C AD - College of Veterinary Medicine and Animal Medical Institute, Chonnam National University, Gwangju 500-757, South Korea. Electronic address: moonc@chonnam.ac.kr. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140201 PL - United States TA - Exp Neurol JT - Experimental neurology JID - 0370712 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Cytokines) RN - 0 (Glial Cell Line-Derived Neurotrophic Factor) RN - 0 (RNA, Messenger) RN - EC 1.14.13.39 (Nitric Oxide Synthase Type II) RN - EC 1.14.13.39 (Nos2 protein, mouse) RN - EC 1.14.99.- (Ptgs2 protein, mouse) RN - EC 1.14.99.1 (Cyclooxygenase 2) SB - IM MH - Animals MH - Brain Diseases/etiology/*physiopathology MH - Brain-Derived Neurotrophic Factor/genetics/metabolism MH - Cyclooxygenase 2/genetics/metabolism MH - Cytokines/genetics/metabolism MH - Depression/etiology/physiopathology MH - Down-Regulation/genetics/radiation effects MH - Glial Cell Line-Derived Neurotrophic Factor/genetics/metabolism MH - Hippocampus/cytology/*physiopathology/*radiation effects MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Microglia/physiology/radiation effects MH - Neurogenesis/physiology/*radiation effects MH - Nitric Oxide Synthase Type II/genetics/metabolism MH - RNA, Messenger/metabolism MH - Radiation Injuries/complications/*physiopathology MH - Radiation, Ionizing OTO - NOTNLM OT - Depression-like behavior OT - Hippocampus OT - Ionizing radiation OT - Microglia OT - Neurogenesis OT - Neurotrophic factor EDAT- 2014/02/05 06:00 MHDA- 2014/05/20 06:00 CRDT- 2014/02/05 06:00 PHST- 2013/12/05 00:00 [received] PHST- 2014/01/21 00:00 [revised] PHST- 2014/01/26 00:00 [accepted] PHST- 2014/02/05 06:00 [entrez] PHST- 2014/02/05 06:00 [pubmed] PHST- 2014/05/20 06:00 [medline] AID - S0014-4886(14)00031-4 [pii] AID - 10.1016/j.expneurol.2014.01.018 [doi] PST - ppublish SO - Exp Neurol. 2014 Apr;254:134-44. doi: 10.1016/j.expneurol.2014.01.018. Epub 2014 Feb 1.