Yang Shan,Wu Lianlian,Guo Wen,Ding Yunhe,Dong Haibei,Wu Xiaojin.Bifidobacterium animalis subsp. lactis BB-12 alleviates hippocampal neuroinflammation and cognitive dysfunction of mice after whole brain irradiation[J].Chinese Journal of Radiological Medicine and Protection,2022,42(11):823-829
Bifidobacterium animalis subsp. lactis BB-12 alleviates hippocampal neuroinflammation and cognitive dysfunction of mice after whole brain irradiation
Received:June 21, 2022  
DOI:10.3760/cma.j.cn112271-20220621-00260
KeyWords:Radiation induced brain injury  Cognitive dysfunction  Glial cell  Neuroinflammation  Bifidobacterium animalis subsp. lactis
FundProject:吴阶平医学基金(320.6750.2021-13-3);徐州医科大学附属医院发展基金(XYFZ2020003)
Author NameAffiliationE-mail
Yang Shan School of Chemical Engineering & Technology, China University of Mining and Technology, Xuzhou 221116, China  
Wu Lianlian Animal Center of Xuzhou Medical University, Xuzhou 221004, China  
Guo Wen Department of Radiation Oncology, Xuzhou First People's Hospital, Affiliated Hospital of China University of Mining and Technology, Xuzhou 221002, China  
Ding Yunhe Department of Radiation Oncology, Xuzhou First People's Hospital, Affiliated Hospital of China University of Mining and Technology, Xuzhou 221002, China  
Dong Haibei Department of Radiation Oncology, Xuzhou First People's Hospital, Affiliated Hospital of China University of Mining and Technology, Xuzhou 221002, China  
Wu Xiaojin Department of Radiation Oncology, Xuzhou First People's Hospital, Affiliated Hospital of China University of Mining and Technology, Xuzhou 221002, China xiaojinwuxz@163.com 
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Abstract::
      Objective To investigate the effects of Bifidobacterium animalis subsp. lactis BB-12 on hippocampal neuroinflammation and cognitive function of mice after whole brain radiotherapy.Methods A total of sixty male C57BL/6J mice aged 7-8 weeks were randomly divided into 5 groups with 12 mice in each group: control group (Con group), probiotic group (BB-12 group), irradiation group (IR group), irradiation and Memantine group (IR+Memantine group), irradiation and probiotic group (IR+BB-12 group). The model of radiation-induced brain injury of mice was established by 10 Gy whole brain radiotherapy with a medical linear accelerator. Y-maze test was used to evaluate the cognitive function. The activation of microglia and astrocytes was observed by immunofluorescence staining. The expressions of inflammatory cytokines interleukin-1β (IL-1β), IL-6 and tumor necrosis factor-α (TNF-α) were detected by quantitative real-time reverse transcription polymerase chain reaction (QRT-PCR) and Western blot.Results Y-maze test showed that, compared with Con group, the percentage of the times of reaching the novel arm in the total times of the three arms decreased significantly in the IR group (t=5.04, P<0.05). BB-12 mitigated radiation-induced cognitive dysfunction (t=4.72, P<0.05). Compared with Con group, the number (t=3.05, 7.18, P<0.05) and circularity index (t=6.23, 2.52, P<0.05) of Iba1 and GFAP positive cells were increased, the microglia and astrocytes were activated in the hippocampus of IR group, but these alterations were eliminated by BB-12. After whole brain IR, the mRNA and protein expression levels of inflammatory cytokines IL-1β, IL-6 and TNF-α in the hippocampus of mice were significantly increased compared with Con group (tmRNA =4.10, 3.04, 4.18, P<0.05; tprotein=11.49, 7.04, 8.42, P<0.05), which were also significantly reduced by BB-12 compared with IR group (tmRNA=4.20, 3.40, 2.84, P<0.05; tprotein=6.36, 4.03, 3.75, P<0.05).Conclusions Bifidobacterium animalis BB-12 can suppress neuroinflammation mediated by microglia and astrocytes in the hippocampus of mice after radiotherapy and alleviates IR-induced cognitive dysfunction. Therefore, BB-12 has potential application in alleviating radiation induced brain injury.
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