title: Possible involvement of hippocampal immediate-early genes in contextual fear memory deficit induced by cranial irradiation.
abstract: Cranial irradiation can trigger adverse effects on brain functions, including cognitive ability. However, the cellular and molecular mechanisms underlying radiation-induced cognitive impairments remain still unknown. Immediate-early genes (IEGs) are implicated in neuronal plasticity and the related functions (i.e., memory formation) in the hippocampus. The present study quantitatively assessed changes in the mRNA and protein levels of the learning-induced IEGs, including Arc, c-fos, and zif268, in the mouse hippocampus after cranial irradiation using quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) and immunohistochemistry, respectively. Mice (male, 8-week-old C57BL/6) received whole-brain irradiation with 0 or 10Gy of gamma-ray and, 2weeks later, contextual fear conditioning (CFC) was used to induce IEGs. In the CFC task, mice evaluated 2weeks after irradiation exhibited significant memory deficits compared with sham (0Gy)-irradiated controls. The levels of mRNA encoding IEGs were significantly upregulated in the hippocampus 10 and 30min after CFC training. The mRNA levels in the irradiated hippocampi were significantly lower than those in the sham-irradiated controls. The IEG protein levels were significantly increased in all hippocampal regions, including the hippocampal dentate gyrus, cornu ammonis (CA)1, and CA3, after CFC training. The CFC-induced upregulation of Arc and c-fos in 10Gy-irradiated hippocampi was significantly lower than that in sham-irradiated controls, although there were no significant differences in the protein levels of the learning-induced zif268 between sham-irradiated and 10Gy-irradiated hippocampi. Thus, cranial irradiation with 10Gy of gamma-ray impairs the induction of hippocampal IEGs (particularly Arc and c-fos) via behavioral contextual fear memory, and this disturbance may be associated with the memory deficits evident in mice after cranial irradiation, possibly through the dysregulation of neuronal plasticity during memory formation.
authors.affiliation: Department of Veterinary Anatomy, College of Veterinary Medicine and Animal Medical Institute, BK21Plus Project Team, Chonnam National University, Gwangju 61186, South Korea.
authors.forename: Yeonghoon
authors.initials: Y
authors.lastname: Son
authors.affiliation: Department of Veterinary Anatomy, College of Veterinary Medicine and Animal Medical Institute, BK21Plus Project Team, Chonnam National University, Gwangju 61186, South Korea.
authors.forename: Sohi
authors.initials: S
authors.lastname: Kang
authors.affiliation: Department of Veterinary Anatomy, College of Veterinary Medicine and Animal Medical Institute, BK21Plus Project Team, Chonnam National University, Gwangju 61186, South Korea.
authors.forename: Jinwook
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Veterinary Anatomy, College of Veterinary Medicine and Animal Medical Institute, BK21Plus Project Team, Chonnam National University, Gwangju 61186, South Korea.
authors.forename: Sueun
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Veterinary Anatomy, College of Veterinary Medicine and Animal Medical Institute, BK21Plus Project Team, Chonnam National University, Gwangju 61186, South Korea.
authors.forename: Jong-Choon
authors.initials: JC
authors.lastname: Kim
authors.affiliation: Department of Veterinary Anatomy, College of Veterinary Medicine and Animal Medical Institute, BK21Plus Project Team, Chonnam National University, Gwangju 61186, South Korea.
authors.forename: Sung-Ho
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Research Center, Dongnam Institute of Radiological & Medical Sciences (DIRAMS), Busan 46033, South Korea.
authors.forename: Joong-Sun
authors.initials: JS
authors.lastname: Kim
authors.affiliation: Radiation Research Division for Bio-Technology Institute, Jeongeup Campus of Korea Atomic Energy Research Institute, Jeonbuk 56212, South Korea.
authors.forename: Sung-Kee
authors.initials: SK
authors.lastname: Jo
authors.affiliation: Radiation Research Division for Bio-Technology Institute, Jeongeup Campus of Korea Atomic Energy Research Institute, Jeonbuk 56212, South Korea.
authors.forename: Uhee
authors.initials: U
authors.lastname: Jung
authors.affiliation: Department of Integrated Biological Science, Pusan National University, Busan 46241, South Korea.
authors.forename: BuHyun
authors.initials: B
authors.lastname: Youn
authors.affiliation: Department of Veterinary Anatomy, College of Veterinary Medicine, Jeju National University, Jeju 63243, South Korea.
authors.forename: Taekyun
authors.initials: T
authors.lastname: Shin
authors.affiliation: Department of Anatomy, School of Medicine and Institute for Environmental Science, Wonkwang University, Jeonbuk 54538, South Korea. Electronic address: yangm@wku.ac.kr.
authors.forename: Miyoung
authors.initials: M
authors.lastname: Yang
authors.affiliation: Department of Veterinary Anatomy, College of Veterinary Medicine and Animal Medical Institute, BK21Plus Project Team, Chonnam National University, Gwangju 61186, South Korea. Electronic address: moonc@chonnam.ac.kr.
authors.forename: Changjong
authors.initials: C
authors.lastname: Moon
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D003214:Conditioning, Classical / Q000502:physiology; D016371:Cranial Irradiation / Q000009:adverse effects*; D005239:Fear / Q000502:physiology*; D017781:Genes, Immediate-Early / Q000502:physiology*; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D008569:Memory Disorders / Q000209:etiology* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL
keywords: Arc; Cranial irradiation; Hippocampus; Memory deficit; c-fos; zif268