多巴胺受体在微波辐射后小鼠认知功能中的作用研究  

Study of the role of dopamine receptors in cognitive function in mice after microwave radiation

作　　者：潘婷 何钢华 冯志华 郝延辉 李杨 左红艳 杜丽娜 PAN Ting;HE Ganghua;FENG Zhihua;HAO Yanhui;LI Yang;ZUO Hongyan;DU Lina(School of Pharmacy,Henan University,Kaifeng 475004,China;Beijing Institute of Radiation Medicine,Academy of Military Medical Science,Beijing 100850,China)

机构地区：[1]河南大学药学院,河南开封475004 [2]军事科学院军事医学研究院辐射医学研究所,北京100850

出　　处：《沈阳药科大学学报》2025年第1期86-93,共8页Journal of Shenyang Pharmaceutical University

基　　金：北京市自然科学基金资助项目(7222250)。

摘　　要：目的研究微波辐射对海马多巴胺能神经元活性的影响及辐射作用敏感的多巴胺受体亚型,探讨多巴胺D4受体(Drd4)特异性拮抗剂对微波辐射致小鼠认知功能改变的影响。方法以C57 BL/6 N小鼠为实验对象,采用2.856 GHz、8 mW·cm^(-2)、比吸收率为6.12 W·kg^(-1)的微波全身辐射小鼠15 min,建立微波辐射小鼠模型。采用免疫荧光技术检测微波辐射对海马各亚区多巴胺能神经元活性的影响。采用实时荧光定量聚合酶联式反应(RT-qPCR)筛选微波辐射敏感的海马多巴胺受体亚型。针对微波辐射敏感的Drd4,采用腹腔注射给予Drd4特异性拮抗剂L-745870(10 mg·kg^(-1)),结合新物体识别行为学实验,研究L-745870对微波辐射致小鼠认知功能改变的影响。结果微波辐射后6 h,海马CA3区多巴胺能神经元活性较对照组显著升高(P<0.01),海马Drd1、Drd4表达较对照组上调(P<0.05、P<0.01)。新物体识别实验结果表明,辐射后1 h,辐射组小鼠新物体辨别指数及认知指数均较对照组降低(P<0.05),而辐射给药组小鼠的新物体辨别指数及认知指数均较辐射组升高(P<0.05)。结论微波辐射可引起海马CA3区多巴胺能神经元活性增强,海马组织Drd1和Drd4基因表达上调,Drd4特异性拮抗剂L-745870可明显改善微波辐射所致认知功能下降。Objective To investigate the effect of microwave radiation on the activity of hippocampal dopaminergic neurons and the radiation-sensitive dopamine receptor subtypes,and to investigate the effect of dopamine D4 receptor(Drd4)-specific antagonists on the cognitive function changes induced by microwave radiation in mice.Methods C57 BL/6 N mice were used as experimental objects,and the whole body of mice were exposed to 2.856 GHz,8 mW·cm^(-2)microwave radiation for 15 min,with a SAR value of 6.12 W·kg^(-1),and the animal model of microwave radiation was established.Immunofluorescence was used to detect the activity of dopaminergic neurons in various subregions of the hippocampus influenced by microwave radiation.Quantitative real-time polymerase reaction(RT-qPCR)was used to screen microwave radiation-sensitive hippocampal dopamine receptor subtypes.For the microwave radiation-sensitive Drd4,the Drd4-specific antagonist L-745870(10 mg·kg^(-1))was administered intraperitoneally,and the effect of L-745870 on the changes of cognitive function in mice induced by microwave radiation was studied in combination with novel object recognition behavior experiments.Results At 6 h after microwave radiation,the activity of dopaminergic neurons in the CA3 region of the hippocampus was significantly increased than that of the control group(P<0.01),and the expressions of Drd1 and Drd4 in the hippocampus was up-regulated compared with that of the control group(P<0.05,P<0.01).The results of new object recognition experiment showed that the novel object discrimination index and recognition index of mice in the radiation group decreased,compared with that in the control group at 1 h after radiation(P<0.05),while the novel object discrimination index and recognition index of mice in the radiation administration group increased than those in the radiation group(P<0.05).Conclusion Microwave radiation can increase the activity of dopaminergic neurons in hippocampal CA3 subregion,up-regulate the expressions of Drd1 and Drd4 in hippocampus

关 键 词：微波辐射 海马 多巴胺能神经元 多巴胺受体 认知功能 

分 类 号：R96[医药卫生—药理学]