Journal of Radiation Research and Radiation Processing ›› 2019, Vol. 37 ›› Issue (4): 2-040301-8.doi: 10.11889/j.1000-3436.2019.rrj.37.040301

• RADIOBIOLOGY AND RADIOMEDICINE • Previous Articles     Next Articles

Ionizing radiation induces cognitive dysfunction by activating prefrontal cortex NLRP3 inflammasome in mice

NAI Aitao1(),WANG Zhen2,LUO Dan3,WANG Yixuan2,WAN Wei2,CAO Wenyu2,HE Jie3,CHEN Xi2,HE Shuya4,WANG Wuzhou4,XU Yang5(),AI Xiaohong1()   

  1. 1. Department of Radiation Oncology, the First Affiliated Hospital of University of South China, Hengyang 421001, China
    2. Clinical Anatomy & Reproductive Medicine Application Institute, Medical College, University of South China, Hengyang 421001, China
    3. Department of Pathology, Medical College, University of South China, Hengyang 421001, China
    4. Department of Radiation Medicine, School of Public Health, University of South China, Hengyang 421001, China
    5. Department of Physiology, Medical College, University of South China, Hengyang 421001, China
  • Received:2019-01-03 Revised:2019-04-11 Accepted:2019-04-11 Online:2019-08-20 Published:2019-08-21
  • Contact: Yang XU,Xiaohong AI E-mail:499108712@qq.com;xuyang2117@163.com;116304926@qq.com
  • About author:NAI Aitao(male) was born in July 1992, and graduated from University of South China in 2015. Now he is a master candidate at the Department of Radiation Oncology, the First Affiliated Hospital of University of South China. E-mail: 499108712@qq.com
  • Supported by:
    the Natural Science Foundation of Hunan Province of China(2018JJ3460);the Education Department Foundation of Hunan Province of China(16A187);the Start-up Funds for PhDs in the University of South China(2015XQD27);Applied Anatomy and Reproductive Medicine Key Laboratory Construction Project in Hengyang(2017KJ182);the Research-based Learning and Innovation Experimental Project for Undergraduate Student of the University of South China(2018XJXZ390);Hunan Provincial Innovation Foundation for Postgraduate(CX2018B638)

Abstract:

To explore the potential mechanism of cognitive impairment induced by ionizing radiation, twenty Kunming female mice were randomly divided into control group and irradiation group. The mice in the irradiation group received a single whole body irradiation of 137Cs γ-rays at an absorbed dose of 4 Gy. The novel object recognition test was used to evaluate the cognitive function of mice 35 d after irradiation. The expression of the microglial marker ionized calcium binding adapter molecule-1 (IBA-1) in the prefrontal cortex was determined by immunohistochemical staining. Western blot was used to detect the expression of nucleotide-binding oligomerization domain such as receptor protein 3 (NLRP3), apoptosis-associated speck-like protein (ASC), cysteinyl aspartate specific proteinase-1 (Caspase-1), interleukin (IL)-1β, and IL-18 protein in the prefrontal cortex. The expression of IBA-1, NLRP3, ASC, and Caspase-1 mRNA in the prefrontal cortex was determined by reverse transcription polymerase chain reaction. The results showed that compared with the control group, the mice in the irradiation group had a low discrimination ratio in the novel object recognition test (38.39 ± 3.69 vs. 28.82 ± 2.08, p<0.05), had higher number of IBA-1 positive cells (138.2 ± 3.7 vs. 159.6 ± 6.9, p<0.05), and remarkably enhanced expression levels of NLRP3, ASC, Caspase-1 protein (1.000 ± 0.066 vs. 1.341 ± 0.119, p<0.05; 1.000 ± 0.073 vs. 1.298 ± 0.083, p<0.05; 1.000 ± 0.039 vs. 1.603 ± 0.159, p<0.01), and NLRP3 and ASC mRNA in the prefrontal cortex (1.000 ± 0.046 vs. 1.372 ± 0.071, p<0.01; 1.000 ± 0.068 vs. 1.225 ± 0.069, p<0.05). Meanwhile, compared with the control group, the expression of inflammatory factors IL-1β and IL-18 was up-regulated in the irradiation group (1.000 ± 0.033 vs. 1.167 ± 0.059, p<0.05; 1.000 ± 0.196 vs. 1.614 ± 0.163, p<0.05). The results indicate that ionizing radiation may induce cognitive dysfunction by activating the NLRP3 inflammasome in the prefrontal cortex of mice.

Key words: Ionizing radiation, Prefrontal cortex, NLRP3 inflammasome, Cognitive dysfunction

CLC Number: 

  • R818.74