PMID- 25792232 OWN - NLM STAT- MEDLINE DCOM- 20160122 LR - 20220409 IS - 1095-9564 (Electronic) IS - 1074-7427 (Linking) VI - 121 DP - 2015 May TI - Cranial irradiation regulates CREB-BDNF signaling and variant BDNF transcript levels in the mouse hippocampus. PG - 12-9 LID - S1074-7427(15)00041-6 [pii] LID - 10.1016/j.nlm.2015.03.002 [doi] AB - The brain can be exposed to ionizing radiation in various ways, and such irradiation can trigger adverse effects, particularly on learning and memory. However, the precise mechanisms of cognitive impairments induced by cranial irradiation remain unknown. In the hippocampus, brain-derived neurotrophic factor (BDNF) plays roles in neurogenesis, neuronal survival, neuronal differentiation, and synaptic plasticity. The significance of BDNF transcript variants in these contexts is becoming clearer. In the present study, both object recognition memory and contextual fear conditioning task performance in adult C57BL/6 mice were assessed 1 month after a single exposure to cranial irradiation (10 Gy) to evaluate hippocampus-related behavioral dysfunction following such irradiation. Furthermore, changes in the levels of BDNF, the cAMP-response element binding protein (CREB) phosphorylation, and BDNF transcript variants were measured in the hippocampus 1 month after cranial irradiation. On object recognition memory and contextual fear conditioning tasks, mice evaluated 1 month after irradiation exhibited significant memory deficits compared to sham-irradiated controls, but no apparent change was evident in locomotor activity. Both phosphorylated CREB and BDNF protein levels were significantly downregulated after irradiation of the hippocampus. Moreover, the levels of mRNAs encoding common BDNF transcripts, and exons IIC, III, IV, VII, VIII, and IXA, were significantly downregulated after irradiation. The reductions in CREB phosphorylation and BDNF expression induced by differential regulation of BDNF hippocampal exon transcripts may be associated with the memory deficits evident in mice after cranial irradiation. CI - Copyright (c) 2015 Elsevier Inc. All rights reserved. FAU - Son, Yeonghoon AU - Son Y AD - Department of Veterinary Anatomy, College of Veterinary Medicine, Chonnam National University, Gwangju 500-757, South Korea. FAU - Yang, Miyoung AU - Yang M AD - Department of Physiology and Neuroscience Program, Michigan State University, East Lansing, MI 48824, USA; Department of Anatomy, School of Medicine, Wonkwang University, Jeonbuk 570-740, South Korea. FAU - Kang, Sohi AU - Kang S AD - Department of Veterinary Anatomy, College of Veterinary Medicine, Chonnam National University, Gwangju 500-757, South Korea. FAU - Lee, Sueun AU - Lee S AD - Department of Veterinary Anatomy, College of Veterinary Medicine, Chonnam National University, Gwangju 500-757, South Korea. FAU - Kim, Jinwook AU - Kim J AD - Department of Veterinary Anatomy, College of Veterinary Medicine, Chonnam National University, Gwangju 500-757, South Korea. FAU - Kim, Juhwan AU - Kim J AD - Department of Veterinary Anatomy, College of Veterinary Medicine, Chonnam National University, Gwangju 500-757, South Korea. FAU - Park, Seri AU - Park S AD - Department of Veterinary Anatomy, College of Veterinary Medicine, Chonnam National University, Gwangju 500-757, South Korea. FAU - Kim, Joong-Sun AU - Kim JS AD - Research center, Dongnam Institute of Radiological & Medical Sciences (DIRAMS), Busan 619-953, South Korea. 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 - Shin, Taekyun AU - Shin T AD - Department of Veterinary Anatomy, College of Veterinary Medicine, Jeju National University, Jeju 690-756, South Korea. FAU - Kim, Sung-Ho AU - Kim SH AD - Department of Veterinary Anatomy, College of Veterinary Medicine, Chonnam National University, Gwangju 500-757, South Korea. FAU - Wang, Hongbing AU - Wang H AD - Department of Physiology and Neuroscience Program, Michigan State University, East Lansing, MI 48824, USA. FAU - Moon, Changjong AU - Moon C AD - Department of Veterinary Anatomy, College of Veterinary Medicine, 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 - 20150316 PL - United States TA - Neurobiol Learn Mem JT - Neurobiology of learning and memory JID - 9508166 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Cyclic AMP Response Element-Binding Protein) RN - 0 (RNA, Messenger) SB - IM MH - Animals MH - Brain/metabolism/radiation effects MH - Brain-Derived Neurotrophic Factor/metabolism/*radiation effects MH - Conditioning, Classical/physiology/*radiation effects MH - Cyclic AMP Response Element-Binding Protein/metabolism/*radiation effects MH - Fear/physiology/radiation effects MH - Hippocampus/metabolism/*radiation effects MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Motor Activity/radiation effects MH - Phosphorylation MH - RNA, Messenger/metabolism/radiation effects MH - Recognition, Psychology/physiology/*radiation effects MH - Signal Transduction/radiation effects OTO - NOTNLM OT - BDNF OT - CREB OT - Cranial irradiation OT - Exon OT - Hippocampus OT - Memory deficit EDAT- 2015/03/21 06:00 MHDA- 2016/01/23 06:00 CRDT- 2015/03/21 06:00 PHST- 2014/10/07 00:00 [received] PHST- 2015/02/25 00:00 [revised] PHST- 2015/03/03 00:00 [accepted] PHST- 2015/03/21 06:00 [entrez] PHST- 2015/03/21 06:00 [pubmed] PHST- 2016/01/23 06:00 [medline] AID - S1074-7427(15)00041-6 [pii] AID - 10.1016/j.nlm.2015.03.002 [doi] PST - ppublish SO - Neurobiol Learn Mem. 2015 May;121:12-9. doi: 10.1016/j.nlm.2015.03.002. Epub 2015 Mar 16.