南方医科大学学报

南方医科大学学报 ›› 2023, Vol. 43 ›› Issue (6): 1041-1046.doi: 10.12122/j.issn.1673-4254.2023.06.22

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抑郁样小鼠额叶体积的减少与脑源性神经营养因子表达的下降有关

崔维维，龚莉雅，陈纯辉，唐佳渝，金 欣，李紫欣，靖林林，文 戈   

  1. 南方医科大学南方医院影像中心，广东 广州 510515；南方医科大学第一临床医学院，广东 广州 510515；广州中医药大学第二附属医院，广东 广州 510120；南方医科大学中西医结合医院手术室，广东 广州 510315
  • 出版日期:2023-06-20 发布日期:2023-07-06

Structural changes of the frontal cortex in depressed mice are associated with decreased expression of brain-derived neurotrophic factor

CUI Weiwei, GONG Liya, CHEN Chunhui, TANG Jiayu, JIN Xin, LI Zixin, JING Linlin, WEN Ge   

  1. Medical Imaging Center, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China; First Clinical Medical College Southern Medical University, Guangzhou 510515,China; Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, China; Operating Theater, TCM Integrated Hospital of Southern Medical University, Guangzhou 510315, China
  • Online:2023-06-20 Published:2023-07-06

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摘要： 目的 研究抑郁样小鼠灰质体积的变化及其可能的内在机制。方法 将24只6周龄C57小鼠随机分为对照组（n=12）与造模组（n=12），利用慢性不可预知温和刺激（CUMS）对小鼠进行35 d的抑郁造模。通过小动物磁共振对两组小鼠进行成像,观察抑郁小鼠较对照组小鼠灰质体积的结构变化。利用免疫印迹与免疫荧光染色的方法观察小鼠相应皮质脑源性神经营养因子（BDNF）的表达情况。结果 造模组小鼠较对照组小鼠在矿场实验中在中央位置的行走距离下降（P<0.05），在强迫游泳实验中不动时间增加（P<0.05）。小动物磁共振成像结果显示，造模组小鼠的额叶皮质体积下降（P<0.001，当团块水平≥10756时，过P=0.05的FDRc矫正）。在蛋白印迹实验中，额叶皮质内成熟BDNF的表达下降（P<0.05）；免疫荧光染色显示，BDNF 在造模后表达下降，并且VBM 分析得到的差异团块的体积大小与蛋白印迹实验中成熟BDNF 表达水平的高低存在相关（P<0.05）。结论 抑郁造模后小鼠额叶皮质体积的下降与额叶皮质内成熟BDNF 表达下降有关。

关键词: 慢性不可预知温和刺激；基于体素的形态学方法；脑源性神经营养因子

Abstract: Objective To investigate the changes in gray matter volume in depressive-like mice and explore the possible mechanism. Methods Twenty- four 6-week-old C57 mice were randomized equally into control group and model group, and the mice in the model group were subjected to chronic unpredictable mild stimulation (CUMS) for 35 days. Magnetic resonance imaging was performed to examine structural changes of the grey matter volume in depressive-like mice. The expression of brain-derived neurotrophic factor (BDNF) in the grey matter of the mice was detected using Western blotting and immunofluorescence staining. Results Compared with the control mice, the mice with CUMS showed significantly decreased central walking distance in the open field test (P<0.05) and increased immobile time in forced swimming test (P<0.05). Magnetic resonance imaging showed that the volume of the frontal cortex was significantly decreased in CUMS mice (P<0.001, when the mass level was greater than or equal to 10 756, the FDRc was corrected with P=0.05). Western blotting showed that the expression of mature BDNF in the frontal cortex was significantly decreased in CUMS mice (P<0.05), and its expression began to decrease after the exposure to CUMS as shown by immunofluorescence staining. The volume of different clusters obtained by voxel-based morphometry (VBM) analysis was correlated with the expression level of mature BDNF detected by Western blotting (P<0.05). Conclusion The decrease of frontal cortex volume after CUMS is related with the reduction of mature BDNF expression in the frontal cortex.

Key words: chronic unpredictable mild stimulation; voxel-based morphometry; brain-derived neurotrophic factor