海马脑源性神经营养因子前体在社会隔离所致小鼠认知障碍中的作用

邓颖成; 牛磊; 肖玉花; 孙秋敏; 徐璇; 万炜

doi:10.16098/j.issn.0529-1356.2022.02.003

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解剖学报 ›› 2022, Vol. 53 ›› Issue (2) : 155-159. DOI: 10.16098/j.issn.0529-1356.2022.02.003

神经生物学

海马脑源性神经营养因子前体在社会隔离所致小鼠认知障碍中的作用

邓颖成¹牛磊¹ 肖玉花¹ 徐璇¹孙秋敏² 万炜^1,3*

作者信息 +

Effect of hippocampal brain derived neurotrophic factor precursor in mice cognitive dysfuction induced by social isolation

DENG Ying-cheng¹ NIU lei¹ XIAO Yu-hua¹ XU Xuan¹ SUN Qiu-ming² WAN Wei^1,3*

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文章历史 +

摘要

目的探讨海马脑源性神经营养因子前体（proBDNF）在社会隔离所致小鼠认知障碍中的作用。方法 30只4周龄C57BL/6 J雄性小鼠随机分成正常群居组(GH，n=15)和社会隔离组(SI，n=15)。各组于相同的环境饲养，GH组5只/笼，SI组1只/笼。采用新旧事物识别和新旧位置识别实验检测小鼠认知功能。Real-time PCR检测各组小鼠海马脑源性神经营养因子(BDNF) mRNA 表达变化。Western blotting检测海马组织BDNF及proBDNF蛋白表达。基质金属蛋白酶9 (MMP-9)、组织型纤溶酶原激活剂(tPA)是胞外酶，可催化proBDNF转化为成熟BDNF。Real-time PCR检测BDNF转化酶MMP-9和tPA mRNA 表达变化。结果行为学结果显示，与 GH 组相比，SI组小鼠新事物分辨率及新位置分辨率明显下降(P<0.01)。Real-time PCR结果显示，与 GH 组相比，SI组小鼠海马中BDNF mRNA的表达差异无显著性。Western blotting结果显示，与 GH 组相比，SI组小鼠海马proBDNF的表达显著上调(P＜0.05)，BDNF的表达差异无显著性；与GH组相比，SI组小鼠海马BDNF/proBDNF的比值降低。此外，Real-time PCR结果显示，与 GH 组相比，SI组小鼠海马中BDNF转化酶MMP-9 mRNA 和tPA mRNA明显下降。结论社会隔离诱导小鼠认知功能障碍可能与海马 proBDNF表达上调有关。

Abstract

Objective To investigate the effect of hippocampal brain derived neurotrophic factor precursor (proBDNF) in cognitive dysfuction induced by social isolation. Methods Thirty C57BL/6 J male mice (4-week old) were randomly divided into group house (GH，n=15) and socially isolated (SI，n=15) groups. The GH group (5 mice/cage) and SI group (1 mice/cage) were reared separately under the same conditions. The novel object recognition test and the novel place recognition test were used to evaluate the cognitive function. The expression of BDNF mRNA in the hippocampus was detected by Real-time PCR. The expression of BDNF and proBDNF in hippocampus was detected by Western blotting. Matrix metallopeptidase-9 (MMP-9) and tissue plasminogen activator (tPA) were extracellular enzymes that catalyzed the transformation of proBDNF into mature BDNF. Expression of MMP-9 and tPA mRNA in the hippocampus were detected by Real-time PCR. Results Compared with the GH group, the SI group showed significantly reduced discrimination ratio in the novel object recognition test and novel place recognition test. The result of Real-time PCR showed that there was no difference in the expression of BDNF mRNA between SI group and GH group. The result of Western blotting showed that the expression level of proBDNF in the hippocampus of SI group increased significantly compared with the GH group (P<0.01),and no difference in BDNF expression was found between the two groups; Compared with the GH group, the BDNF/proBDNF ratio in the hippocampus of SI group decreased. In addition, the result of Real-time PCR showed that the expression level of MMP-9 and tPA mRNA in the hippocampus of SI group decreased significantly compared with the GH group. Conclusion The social isolation-induced cognitive dysfuction in mice may be related to the up-regulation of proBDNF in the hippocampus．

导出引用

邓颖成牛磊肖玉花徐璇孙秋敏万炜. 海马脑源性神经营养因子前体在社会隔离所致小鼠认知障碍中的作用[J]. 解剖学报. 2022, 53(2): 155-159 https://doi.org/10.16098/j.issn.0529-1356.2022.02.003

DENG Ying-cheng NIU lei XIAO Yu-hua XU Xuan SUN Qiu-ming WAN Wei. Effect of hippocampal brain derived neurotrophic factor precursor in mice cognitive dysfuction induced by social isolation[J]. Acta Anatomica Sinica. 2022, 53(2): 155-159 https://doi.org/10.16098/j.issn.0529-1356.2022.02.003

中图分类号： R322.81

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