Wu Qiong,Yuan Lei,Yu Min,Liu Zhenghai,Wang Zhen,Yang Hui,Li Cai,Ai Xiaohong,He Jie,Wan Wei.Effect of intermittent fasting on the cognitive dysfunction induced by irradiation[J].Chinese Journal of Radiological Medicine and Protection,2022,42(5):335-342
Effect of intermittent fasting on the cognitive dysfunction induced by irradiation
Received:December 14, 2021  
DOI:10.3760/cma.j.cn112271-20211214-00483
KeyWords:Irradiation  Intermittent fasting  Cognitive dysfunction  Autophgy  Recombinant Voltage Dependent Anion Channel Protein 1 (VDAC1)
FundProject:湖南省自然科学基金(2021JJ30052,2020JJ4543,2019JJ40257);海南省海南医学院研究生创新课题研究项目(HYYS2020-31)
Author NameAffiliationE-mail
Wu Qiong Key Laboratory of Brain Science Research & Transformation in Tropical Environment of Hainan Province, Haikou 571199, China  
Yuan Lei Key Laboratory of Brain Science Research & Transformation in Tropical Environment of Hainan Province, Haikou 571199, China  
Yu Min Department of Pharmacy, Chenzhou First People's Hospital, Chenzhou 423001, China  
Liu Zhenghai Clinical Anatomy & Reproductive Medicine Application Institute, School of Medicine, University of South China, Hengyang 421001, China  
Wang Zhen Medical College of Hunan Vocational College of Environmental Biology, Hengyang 421001, China  
Yang Hui Department of Pathology, Ganzhou people's Hospital, Ganzhou 341099, China  
Li Cai Clinical Anatomy & Reproductive Medicine Application Institute, School of Medicine, University of South China, Hengyang 421001, China  
Ai Xiaohong Department of Oncology and Radiotherapy, the First Affiliated Hospital of Nanhua University, Hengyang 421001  
He Jie Department of Pathology, Hainan Medical College, Haikou 571199, China  
Wan Wei Key Laboratory of Brain Science Research & Transformation in Tropical Environment of Hainan Province, Haikou 571199, China david-wan@163.com 
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Abstract::
      Objective To investigate the protective effect of intermittent fasting on radiation-induced cognitive impairment and the possible underlying mechanism.Methods A total of 36 male 7-week old c57BL/6J mice were divided into Sham-irradiation and ad libitum (Sham-AL) group, irradiation and ad libitum (IR-AL) group, and irradiation add intermittent fasting (IR-IF) group according to the random number table method, with 12 mice in each group. The cognitive function of mice was assessed by novel object recognition task. The expressions of autophagy gene 5 (ATG5), microtubulesas sociated protein light chain II (LC3II), voltage dependent anion channel protein 1 (VDAC1), interleukin-1β (IL-1β), synaptophysin (SYP), synapsin I (SYN-1), and postsynaptic density 95 (PSD95) were tested by Western blot. The location of VDAC1 in mice hippocampus was detected by immunofluorescence.Results The discrimination index (-22.45 ±16.76) of IR-AL group was significantly (t=3.032,P<0.05) lower than that of Sham-AL group (30.02 ±9.05). Compared to Sham-AL group, IR-AL group had a decreased expressions of autophagy-related proteins (ATG5 and LC3II), mitochondrial marker (VDAC1), inflammatory factors (IL-1β) as well as synapse-associated proteins SYP, SYN-1 and PSD95 (t=2.49, 2.19, 2.40, 3.47, 2.87, 2.25, 2.17, 2.31,P<0.05). Compared to IR-AL group, IR-IF group had an increased discrimination index (21.22 ±5.62) and the increased expressions of ATG5, LC3II, VDAC1, IL-1β, SYP, SYN-1, and PSD95 (t=2.70, 2.88, 2.71, 3.18, 3.18, 3.11, 3.30, 3.35, 2.53,P<0.05). The immunofluorescence assay revealed that VDAC1 was co-expressed with the markers of astrocytes (GFAP) and microglia (IBA-1), but not with neurons (NEUN).Conclusions Intermittent fasting could greatly improve the cognitive function of irradiated mice possibly by upregulating VDAC1 expression, induce autophagy, and inhibit the release of inflammatory factors and protecting the synapticplasticity in the hippocampus.
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