双侧嗅球切除对小鼠行为、海马神经递质及抑郁相关基因表达的影响  

Influence of olfactory bulbectomy on mouse neurobehaviors,hippocampal neurotransmission and depression relevant gene expressions

作　　者：王婷婷[1] 黄菲[1] 吴辉[1] 张蓓蓓[1] 张信诚 吴晓俊[1] 胡之璧[1] 

机构地区：[1]上海市复方中药重点实验室暨上海中医药大学中药研究所,上海201203

出　　处：《中国药理学通报》2015年第5期686-691,共6页Chinese Pharmacological Bulletin

基　　金：教育部高等学校博士学科点专项科研基金优先发展领域项目(No 20123107130002);上海市教委科研创新重点项目(No 13ZZ099);上海高校特聘教授(东方学者)岗位计划资助(No 2013-59)

摘　　要：目的研究双侧嗅球切除对C57BL/6小鼠行为和海马神经递质及抑郁相关基因表达的影响。方法用探针捣毁并用负压吸出小鼠嗅球建立嗅球切除模型,术后18 d开始分别进行强迫游泳、悬尾、旷场、高架迷宫行为学测试,同时应用LC-MS/MS液质联用法检测海马内7种神经递质的变化,实时定量PCR法检测海马抑郁相关基因的表达。结果嗅球切除后小鼠在旷场中的水平运动明显增加(P<0.05),进入高架迷宫开臂的时间明显延长(P<0.01),海马组织中的5-HIAA/5-HT明显降低(P<0.01),Glu/GABA明显增高(P<0.01)。同时海马组织中的BDNF、Trkb、GDNF、CD11b、TNF-α基因表达明显升高(P<0.05),而TPH2基因表达下调(P<0.05)。结论嗅球切除导致小鼠多种行为学改变,是多种神经传递以及神经营养因子、炎症因子和合成蛋白基因综合作用的结果,提示将该模型作为抗抑郁药物的研发及筛选工具时需要综合考虑多方面因素的影响,从而对实验结果作出科学合理解释。Aim To investigate the changes of behav-iors,neurotransmitters and depression related gene ex-pressions in hippocampus of C57BL/6 mice after olfac-tory bulbectomy （OB）.Methods Forced swimming test （FST）,tail suspension test （TST）,open filed test （OFT）,and elevated plus maze test （EPMT） were used to evaluate the behavioral changes 18 days＆nbsp;after surgery. LC-MS/MS method was employed to measure the hippocampal neurotransmitters.Quantita-tive PCR approach was established to determine the hippocampal gene expressions associated with depres-sion.Results OB mice were hyperactive in OFT （P〈0.05 ） accompanied with increased time spent in open arm of EPMT （P〈0.01）.Meanwhile,the sur-gery led to the reduction of the ratio of 5-HIAA/5-HT （P 〈0.01 ） but the increase of Glu/GABA （P 〈0.01 ） in hippocampus.Moreover,OB elevated the gene expressions of BDNF,Trkb,GDNF,CD1 1 b and TNF-αbut down-regulated that of TPH2 in hippocam-pus （P〈0.05 ）.Conclusion Behavioral alternation of OB mice was a result of comprehensive effect of the＆nbsp;changes of neurotransmission and depression related genes,which call us special attention in using OB as an animal model for research and development of anti-depressants.

关 键 词：抑郁 嗅球 神经递质 海马 神经营养因子 炎症因子 抗抑郁药 

分 类 号：R-332[医药卫生] R322.81