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少突胶质细胞在微波辐射致小鼠认知损伤中的作用机制研究OA

Roles of oligodendrocytes in cognitive impairment induced by microwave radiation in mice

中文摘要英文摘要

目的 探讨少突胶质细胞在微波辐射致小鼠认知损伤模型中功能的改变及作用机制.方法 采用频率为2.856 GHz,平均功率密度8 mW/cm2的S波段微波对C57BL/6N雄性小鼠进行全身暴露,单次15 min.采用光纤测温仪监测微波辐射过程中小鼠肛温的变化;采用旷场和新物体识别实验检测辐射后第1、7天小鼠自主探索行为和学习记忆能力的改变情况;采用免疫荧光检测辐射后第1、7天小鼠海马组织中神经胶质抗原2(NG2)和髓鞘碱性蛋白(MBP)的表达和分布;采用促少突胶质前体细胞成熟药物富马酸氯马斯汀灌胃给药,并通过放射免疫法检测辐射后1、7天海马组织中脑源性神经营养因子(BDNF)和成纤维细胞生长因子2(FGF2)表达水平;采用透射电镜法观察辐射后第1、7天胼胝体髓鞘结构的改变情况;通过旷场和新物体识别实验评估富马酸氯马斯汀对微波暴露引起的小鼠学习记忆损伤的干预作用.结果 该实验条件下,微波辐射引起小鼠肛温升高低于1 ℃,在机体热安全范围内.旷场实验显示,与对照组比较,微波辐射后第1、7天小鼠运动速度无显著改变,辐射后第1天中央区域探索时间显著降低(P<0.05);新物体识别实验中,微波辐射后第1天小鼠新物体辨别指数显著降低(P<0.05),提示微波辐射后小鼠产生焦虑样行为和认知功能损伤.与对照组比较,微波辐射后第1天海马组织中NG2+面积占比显著降低(P<0.05),MBP+面积占比无显著变化(P>0.05),海马组织中少突胶质细胞相关BDNF表达水平显著下降(P<0.05),胼胝体髓鞘出现断裂等病理改变,髓鞘g比显著增加(P<0.05),表明微波辐射可引起少突胶质细胞前体数量减少,少突胶质细胞分泌和髓鞘功能损伤.与单独辐射组比较,辐射联合富马酸氯马斯汀用药组小鼠辐射后第1天BNDF、FGF2表达水平有上调趋势,髓鞘g比显著降低(P<0.05),新物体识别中小鼠于辐射后第1天新物体辨别指数显著升高(P<0.05),提示富马酸氯马斯汀可改善微波辐射引起的少突胶质细胞功能损伤和认知功能障碍.结论 低于机体发热阈值的脉冲微波辐射可引起小鼠认知功能障碍等脑损伤,其中,少突胶质细胞分泌和髓鞘功能受损及自我修复能力下降是微波辐射致认知功能障碍的重要机制.

Objective To investigate the functional changes of oligodendrocytes in a mouse model of cognitive impairment induced by microwave radiation and the mechanism.Methods C57BL/6N male mice were exposed to S-band microwave at 2.856 GHz and 8 mW/cm2 for 15 min.The rectal temperature of mice was monitored by an optical fiber thermometer during microwave radiation.The changes of autonomous exploration behavior and learning and memory ability of mice on the 1st and 7th days after microwave radiation were detected via the open field test and novel object recognition test.Immunofluorescence was used to detect the expression and distribution of neuroglia-2 proteoglycan(NG2)and myelin basic protein(MBP)in the hippocampus of mice on the 1st and 7th days after radiation.Clemastine fumarate,a drug that promoted the maturation of oligodendrocyte precursor cells was administered by gavage,and the expression levels of brain-derived neurotrophic factor(BDNF)and fibroblast growth factor 2(FGF2)in hippocampal tissues were detected by radioimmunoassay at 1 and 7 days after radiation.The changes of myelin sheath structure an 1 and 7 days after radiation were observed by transmission electron microscopy.The effects of clemastine fumarate on learning and memory impairment induced by microwave exposure in mice were assessed via open field and new object recognition experiments.Results Under the experimental conditions,the rectal temperature in mice caused by microwave radiation increased by less than 1 ℃,which was within the thermal safety range of the body.The open field test showed that compared with the control group,the microwave radiation group didn't change significant in terms of movement speedon the 1st and 7th days,but the time spent exploring in the central area was significantly reducedon the 1st day after radiation(P<0.05).In the novel object recognition test,the indexes of the mice on the 1st day were significantly reduced(P<0.05),indicating that the anxiety like behavior and cognitive function of the mice were impaired after microwave radiation.Compared with the control group,the proportion of NG2+area in the hippocampus was significantly decreased(P<0.05)in the microwave radiation group,while that of MBP+area hardly changed on the 1st day after microwave radiation(P>0.05).The expression level of oligodendrocyte related BDNF in the hippocampus was significantly decreased(P<0.05).The myelin of the corpus callosum was broken,and the myelin g ratio was significantly increased(P<0.05),suggesting that micro wave radiation could reduce the number of oligodendrocyte precursors and damage the secretion and myelin function of oligodendrocyte.Compared with the radiation group,the expression levels of BNDF and FGF2 in the radiation combined with clemastine fumarate group were up-regulated,the myelin g ratio was significantly decreased on the 1st day after radiation(P<0.05),and the novel object recognition index was significantly increased(P<0.05).Conclusion Pulsed microwave radiation below the body's fever threshold can cause cognitive dysfunction and other brain damage in mice.The impaired secretion and myelin function of oligodendrocytes and the decreased self-repair ability are the important mechanisms of cognitive dysfunction induced by microwave radiation.

王俊;郝延辉;李杨;刘玉杰;杨雪枫;李刻勤;刘莹;杨喆;叶雨萌;刘泽杭;左红艳

安徽医科大学生命科学学院,合肥 230032||军事科学院军事医学研究院,北京 100850军事科学院军事医学研究院,北京 100850安徽医科大学生命科学学院,合肥 230032||军事科学院军事医学研究院,北京 100850军事科学院军事医学研究院,北京 100850安徽医科大学生命科学学院,合肥 230032||军事科学院军事医学研究院,北京 100850军事科学院军事医学研究院,北京 100850军事科学院军事医学研究院,北京 100850军事科学院军事医学研究院,北京 100850军事科学院军事医学研究院,北京 100850军事科学院军事医学研究院,北京 100850军事科学院军事医学研究院,北京 100850

特种医学

微波辐射认知髓鞘少突胶质细胞小鼠

microwave radiationcognitionmyelin sheatholigodendrocytesmice

《军事医学》 2025 (10)

738-746,9

10.7644/j.issn.1674-9960.2025.10.003

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