title: Cranial irradiation regulates CREB-BDNF signaling and variant BDNF transcript levels in the mouse hippocampus.
abstract: 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.
authors: Department of Veterinary Anatomy, College of Veterinary Medicine, Chonnam National University, Gwangju 500-757, South Korea.
authors: Yeonghoon
authors: Y
authors: Son
authors: 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.
authors: Miyoung
authors: M
authors: Yang
authors: Department of Veterinary Anatomy, College of Veterinary Medicine, Chonnam National University, Gwangju 500-757, South Korea.
authors: Sohi
authors: S
authors: Kang
authors: Department of Veterinary Anatomy, College of Veterinary Medicine, Chonnam National University, Gwangju 500-757, South Korea.
authors: Sueun
authors: S
authors: Lee
authors: Department of Veterinary Anatomy, College of Veterinary Medicine, Chonnam National University, Gwangju 500-757, South Korea.
authors: Jinwook
authors: J
authors: Kim
authors: Department of Veterinary Anatomy, College of Veterinary Medicine, Chonnam National University, Gwangju 500-757, South Korea.
authors: Juhwan
authors: J
authors: Kim
authors: Department of Veterinary Anatomy, College of Veterinary Medicine, Chonnam National University, Gwangju 500-757, South Korea.
authors: Seri
authors: S
authors: Park
authors: Research center, Dongnam Institute of Radiological & Medical Sciences (DIRAMS), Busan 619-953, South Korea.
authors: Joong-Sun
authors: JS
authors: Kim
authors: Radiation Research Division for Bio-Technology Institute, Jeongeup Campus of Korea Atomic Energy Research Institute, Jeonbuk 580-185, South Korea.
authors: Sung-Kee
authors: SK
authors: Jo
authors: Radiation Research Division for Bio-Technology Institute, Jeongeup Campus of Korea Atomic Energy Research Institute, Jeonbuk 580-185, South Korea.
authors: Uhee
authors: U
authors: Jung
authors: Department of Veterinary Anatomy, College of Veterinary Medicine, Jeju National University, Jeju 690-756, South Korea.
authors: Taekyun
authors: T
authors: Shin
authors: Department of Veterinary Anatomy, College of Veterinary Medicine, Chonnam National University, Gwangju 500-757, South Korea.
authors: Sung-Ho
authors: SH
authors: Kim
authors: Department of Physiology and Neuroscience Program, Michigan State University, East Lansing, MI 48824, USA.
authors: Hongbing
authors: H
authors: Wang
authors: Department of Veterinary Anatomy, College of Veterinary Medicine, Chonnam National University, Gwangju 500-757, South Korea. Electronic address: moonc@chonnam.ac.kr.
authors: Changjong
authors: C
authors: Moon
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism / Q000528:radiation effects; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism / Q000528:radiation effects*; D003214:Conditioning, Classical / Q000502:physiology / Q000528:radiation effects*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism / Q000528:radiation effects*; D005239:Fear / Q000502:physiology / Q000528:radiation effects; D006624:Hippocampus / Q000378:metabolism / Q000528:radiation effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000528:radiation effects; D010766:Phosphorylation; D012333:RNA, Messenger / Q000378:metabolism / Q000528:radiation effects; D021641:Recognition, Psychology / Q000502:physiology / Q000528:radiation effects*; D015398:Signal Transduction / Q000528:radiation effects
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D017362:Cyclic AMP Response Element-Binding Protein; D012333:RNA, Messenger
keywords: BDNF; CREB; Cranial irradiation; Exon; Hippocampus; Memory deficit