Huang Zhifei,Zhou Guiqiang,Li Jiangyi,et al.Effects and their mechanisms of acute radiation with 60Co γ-rays on the emotional state in exposed mice[J].Chinese Journal of Radiological Medicine and Protection,2025,45(12):1228-1236
Effects and their mechanisms of acute radiation with 60Co γ-rays on the emotional state in exposed mice
Received:January 17, 2025  
DOI:10.3760/cma.j.cn112271-20250117-00023
KeyWords:γ-ray  Mice  Anxiety-like behavior  Pyroptosis  Astrocyte
FundProject:陕西省重点研发计划项目(2024SF-YBXM-437)
Author NameAffiliationE-mail
Huang Zhifei School of Public Health, Shandong Second Medical University, Weifang 261053, China
Ministry-of-Education's Key Laboratory of Hazard Assessment and Control in Special Operational Environment, Department of Radiation Protection Medicine, School of Military Preventive Medicine, Air Force Military Medical University, Xi'an 710032, China 
 
Zhou Guiqiang Ministry-of-Education's Key Laboratory of Hazard Assessment and Control in Special Operational Environment, Department of Radiation Protection Medicine, School of Military Preventive Medicine, Air Force Military Medical University, Xi'an 710032, China  
Li Jiangyi School of Public Health, Shandong Second Medical University, Weifang 261053, China
Ministry-of-Education's Key Laboratory of Hazard Assessment and Control in Special Operational Environment, Department of Radiation Protection Medicine, School of Military Preventive Medicine, Air Force Military Medical University, Xi'an 710032, China 
 
Qin Tongzhou Ministry-of-Education's Key Laboratory of Hazard Assessment and Control in Special Operational Environment, Department of Radiation Protection Medicine, School of Military Preventive Medicine, Air Force Military Medical University, Xi'an 710032, China  
Liu Liyuan Ministry-of-Education's Key Laboratory of Hazard Assessment and Control in Special Operational Environment, Department of Radiation Protection Medicine, School of Military Preventive Medicine, Air Force Military Medical University, Xi'an 710032, China  
Zheng Bo Ministry-of-Education's Key Laboratory of Hazard Assessment and Control in Special Operational Environment, Department of Radiation Protection Medicine, School of Military Preventive Medicine, Air Force Military Medical University, Xi'an 710032, China  
Wang Xing Ministry-of-Education's Key Laboratory of Hazard Assessment and Control in Special Operational Environment, Department of Radiation Protection Medicine, School of Military Preventive Medicine, Air Force Military Medical University, Xi'an 710032, China  
Wang Haonan Ministry-of-Education's Key Laboratory of Hazard Assessment and Control in Special Operational Environment, Department of Radiation Protection Medicine, School of Military Preventive Medicine, Air Force Military Medical University, Xi'an 710032, China  
Wang Chunping School of Public Health, Shandong Second Medical University, Weifang 261053, China  
Ding Guirong Ministry-of-Education's Key Laboratory of Hazard Assessment and Control in Special Operational Environment, Department of Radiation Protection Medicine, School of Military Preventive Medicine, Air Force Military Medical University, Xi'an 710032, China dingzhao@fmmu.edu.cn 
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Abstract::
      Objective To explore the effects and their mechanisms of single whole-body exposure to 60Co γ-rays on the emotional state in mice.Methods Totally 48 male C57BL/6 mice aged 6-8 weeks were randomly divided into a control, a 4 Gy irradiation group, and a 6 Gy irradiation group using the random number table method, with six mice in each group. Mice in the 4 and 6 Gy irradiation groups received a single whole-body irradiation with 60Co γ-rays at a dose rate of 1.91 Gy/min, with doses of 4 Gy and 6 Gy, respectively. Then, behavioral experiments were conducted at 1, 3, and 6 weeks post-irradiation, followed by tissue sampling. The anxiety-like behavior of the mice was assessed using open field test (OFT) and elevated plus maze (EPM). Their depressive-like behavior was assessed using the forced swim test (FST) and tail suspension test (TST), and the morphological and structural changes of their hippocampus were examined using hematoxylin and eosin (HE) and Nissl staining. Furthermore, the expression levels of the astrocyte marker of glial fibrillary acidic protein (GFAP) and the microglial marker of Iba-1 in the hippocampus of the mice were detected using immunohistochemical (IHC) staining. The expression levels of the pyroptosis markers of Gasdermin D (GSDMD) and Cleaved-caspase1 in the hippocampus were examined using immunofluorescence (IF) staining, and the expression levels of GFAP, Iba-1, GSDMD, and Cleaved-caspase1 in the hippocampus were detected by Western blot analysis.Results Compared to the control group, the irradiation groups showed no depressive-like behavior at 6 weeks post-irradiation, but manifested anxiety-like behavior at 3 weeks post-irradiation. Furthermore, the anxiety-like behavior persisted until 6 weeks post-irradiation, with no signs of recovery. Compared to the 4 Gy irradiation group, such an effect was more pronounced in the 6 Gy irradiation group. Pathological result indicate that mice in both irradiation groups showed neuron changes in the hippocampal CA3 region, such as deep staining and nuclear condensation, and the number of damaged neurons increased significantly (F = 50.04, P < 0.05), with more significant changes observed in the 6 Gy irradiation group (t = 2.95, P < 0.05). The IHC and IF staining result showed that, compared to the control group, the 6 Gy irradiation group presented a significant increase in the number of GFAP-positive cells in the hippocampal CA3 region (t = 3.27, P < 0.05). Both irradiation groups displayed significant increases in the numbers of GSDMD and Cleaved-caspase 1 positive cells in the hippocampal CA3 region (F = 55.06, 15.92, P < 0.05), with an upward trend identified in the 6 Gy irradiation group. The Western blot analysis result indicated that, compared to the control group, the 6 Gy irradiation group showed a significant rise in the protein expression level of hippocampal GFAP (t = 2.92, P < 0.05). Both irradiation groups exhibited significantly elevated protein expression levels of hippocampal GSDMD and Cleaved-caspase 1 (F = 5.76, 7.02, P < 0.05).Conclusions Acute whole-body exposure to 4 Gy and 6 Gy 60Co γ-rays can induce anxiety-like behavior in mice, with a certain extent of dose-effect relationship. The hippocampal pyroptosis and astrocyte activation associated with emotional regulation might be involved in the mechanism underlying γ-ray-induced emotional disturbance.
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