Son Yeonghoon, Yang Miyoung, Kang Sohi, Lee Sueun, Kim Jinwook, Kim Juhwan, Park Seri, Kim Joong-Sun, Jo Sung-Kee, Jung Uhee, Shin Taekyun, Kim Sung-Ho, Wang Hongbing, Moon Changjong
Department of Veterinary Anatomy, College of Veterinary Medicine, Chonnam National University, Gwangju 500-757, South Korea.
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.
Neurobiol Learn Mem. 2015 May;121:12-9. doi: 10.1016/j.nlm.2015.03.002. Epub 2015 Mar 16.
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.
大脑可通过多种方式暴露于电离辐射，这种辐射会引发不良影响，尤其是对学习和记忆的影响。然而，颅脑照射所致认知障碍的确切机制仍不清楚。在海马体中，脑源性神经营养因子（BDNF）在神经发生、神经元存活、神经元分化和突触可塑性中发挥作用。BDNF转录变体在这些情况下的意义正变得越来越清晰。在本研究中，对成年C57BL/6小鼠单次进行颅脑照射（10 Gy）1个月后，评估其物体识别记忆和情境恐惧条件反射任务表现，以评价照射后海马体相关的行为功能障碍。此外，在颅脑照射1个月后，检测海马体中BDNF水平、环磷酸腺苷反应元件结合蛋白（CREB）磷酸化水平及BDNF转录变体的变化。在物体识别记忆和情境恐惧条件反射任务中，照射后1个月评估的小鼠与假照射对照组相比表现出明显的记忆缺陷，但运动活性无明显变化。海马体照射后，磷酸化CREB和BDNF蛋白水平均显著下调。此外，编码常见BDNF转录本以及外显子IIC、III、IV、VII、VIII和IXA的mRNA水平在照射后也显著下调。BDNF海马体外显子转录本的差异调节所诱导的CREB磷酸化和BDNF表达降低，可能与小鼠颅脑照射后明显的记忆缺陷有关。
