中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2019, Vol. 14 ›› Issue (9): 1530-1535.doi: 10.4103/1673-5374.255974

• 原著:神经损伤修复保护与再生 • 上一篇    下一篇

丁酸钠可预防电离辐射诱导的认知功能障碍

  

  • 出版日期:2019-09-15 发布日期:2019-09-15
  • 基金资助:

    韩国国家研究基金会（NRF）的核研究与发展计划（NRF-2012M2A2A7012377，NRF-2015M2B2B1068627）和韩国政府科学，ICT和未来规划部国家研究项目（NRF-2015R1C1A2A01053041）

Sodium butyrate prevents radiation-induced cognitive impairment by restoring pCREB/BDNF expression

Hae June Lee 1 , Yeonghoon Son 1, 2 , Minyoung Lee 3 , Changjong Moon 4 , Sung Ho Kim 4 , In Sik Shin 4 , Miyoung Yang 5 , Sangwoo Bae 1 , Joong Sun Kim 6   

  1. 1 Division of Basic Radiation Bioscience, Korea Institute of Radiological & Medical Sciences (KIRMAS), Seoul, Republic of Korea
    2 National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju, Republic of Korea
    3 College of Pharmacy, Kyungpook National University, Daegu, Republic of Korea
    4 College of Veterinary Medicine, Veterinary Medical Research Institute, Chonnam National University, Gwangju, Republic of Korea
    5 School of Medicine, Wonkwang University, Jeonbuk, Republic of Korea
    6 Research Center, Dongnam Institute of Radiological & Medical Sciences (DIRAMS), Busan, Republic of Korea
  • Online:2019-09-15 Published:2019-09-15
  • Contact: Joong Sun Kim, jskim@dirams.re.kr.
  • Supported by:

    This work was supported by the Nuclear Research and Development Program (NRF-2012M2A2A7012377, NRF-2015M2B2B1068627 and NRF-2015R1C1A2A01053041) of the National Research Foundation of Korea (NRF) funded by the Korean Government Ministry of Science, ICT & Future Planning.

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摘要：

丁酸钠是一种可影响多种类型脑损伤的脱乙酰化酶抑制剂。为了解丁酸钠对全脑放疗后的海马功能障碍和电离辐射暴露引起致认知功能障碍的影响，实验在将成年C57BL/6小鼠头部暴露于10Gy电离辐射前，给予其0.6g/kg腹腔注射。在辐射后30d通过物体识别测试评估小鼠的认知功能，免疫组化染色和免疫印迹法检测海马神经发生标记物双皮质素和磷酸化cAMP反应元件结合蛋白/脑源性神经营养因子的表达水平。暴露于辐射的小鼠认知功能降低，海马双皮质素、磷酸化cAMP反应元件结合蛋白/脑源性神经营养因子水平表达水平显著降低。丁酸钠预防性干预可逆转上述变化。从而表明丁酸钠可通过抑制海马磷酸化cAMP反应元件结合蛋白/脑源性神经营养因子水平的降低来预防性改善放射诱导的认知功能障碍。

orcid: 0000-0003-2180-4860 (Joong Sun Kim)

关键词: 丁酸钠, 辐射防护剂, 电离辐射, 海马损伤, cAMP反应元件结合, 脑源性神经营养因子, 组蛋白去乙酰化酶抑制剂, 神经发生

Abstract:

Sodium butyrate is a histone deacetylase inhibitor that affects various types of brain damages. To investigate the effects of sodium butyrate on hippocampal dysfunction that occurs after whole-brain irradiation in animal models and the effect of sodium butyrate on radiation exposure-induced cognitive impairments, adult C57BL/6 mice were intraperitoneally treated with 0.6 g/kg sodium butyrate before exposure to 10 Gy cranial irradiation. Cognitive impairment in adult C57BL/6 mice was evaluated via an object recognition test 30 days after irradiation. We also detected the expression levels of neurogenic cell markers (doublecortin) and phosphorylated cAMP response element binding protein/brain-derived neurotrophic factor. Radiation-exposed mice had decreased cognitive function and hippocampal doublecortin and phosphorylated cAMP response element binding protein/brain-derived neurotrophic factor expression. Sodium butyrate pretreatment reversed these changes. These findings suggest that sodium butyrate can improve radiation-induced cognitive dysfunction through inhibiting the decrease in hippocampal phosphorylated cAMP response element binding protein/brain-derived neurotrophic factor expression. The study procedures were approved by the Institutional Animal Care and Use Committee of Korea Institute of Radiological Medical Sciences (approval No. KIRAMS16-0002) on December 30, 2016.

Key words: sodium butyrate, radioprotector, ionizing radiation, hippocampal damage, cAMP response element binding, brain-derived neurotrophic factor, histone deacetylase inhibitor, neurogenesis