Son Yeonghoon, Kang Sohi, Kim Jinwook, Lee Sueun, Kim Jong-Choon, Kim Sung-Ho, Kim Joong-Sun, Jo Sung-Kee, Jung Uhee, Youn BuHyun, Shin Taekyun, Yang Miyoung, Moon Changjong
Department of Veterinary Anatomy, College of Veterinary Medicine and Animal Medical Institute, BK21Plus Project Team, Chonnam National University, Gwangju 61186, South Korea.
Research Center, Dongnam Institute of Radiological & Medical Sciences (DIRAMS), Busan 46033, South Korea.
Neurobiol Learn Mem. 2016 Sep;133:19-29. doi: 10.1016/j.nlm.2016.05.012. Epub 2016 May 30.
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.
颅脑照射可引发对脑功能的不良影响，包括认知能力。然而，辐射诱导认知障碍背后的细胞和分子机制仍然未知。即刻早期基因（IEGs）与海马体中的神经元可塑性及相关功能（即记忆形成）有关。本研究分别使用定量实时逆转录聚合酶链反应（qRT-PCR）和免疫组织化学方法，定量评估了颅脑照射后小鼠海马体中学习诱导的即刻早期基因（包括Arc、c-fos和zif268）的mRNA和蛋白质水平变化。小鼠（雄性，8周龄C57BL/6）接受0或10Gy的γ射线全脑照射，2周后，采用情境恐惧条件反射（CFC）诱导即刻早期基因。在CFC任务中，照射后2周评估的小鼠与假照射（0Gy）对照组相比表现出明显的记忆缺陷。CFC训练后10分钟和30分钟，海马体中编码即刻早期基因的mRNA水平显著上调。照射后海马体中的mRNA水平显著低于假照射对照组。CFC训练后，包括海马齿状回、海马角（CA）1和CA3在内的所有海马区域的即刻早期基因蛋白水平均显著增加。尽管假照射和10Gy照射的海马体中学习诱导的zif268蛋白水平没有显著差异，但10Gy照射的海马体中CFC诱导的Arc和c-fos上调明显低于假照射对照组。因此，10Gy的γ射线颅脑照射通过行为情境恐惧记忆损害海马体即刻早期基因（特别是Arc和c-fos）的诱导，这种干扰可能与颅脑照射后小鼠明显的记忆缺陷有关，可能是通过记忆形成过程中神经元可塑性的失调。
