基础医学与临床 ›› 2024, Vol. 44 ›› Issue (6): 809-815.doi: 10.16352/j.issn.1001-6325.2024.06.0809

• 研究论文 • 上一篇    下一篇

文拉法辛提升抑郁模型小鼠的神经元轴突结构稳定性

隋家平, 韦晖*   

  1. 中国医学科学院基础医学研究所 北京协和医学院基础学院 重大疾病共性机制研究全国重点实验室,北京 100005
  • 收稿日期:2024-03-06 修回日期:2024-04-24 出版日期:2024-06-05 发布日期:2024-05-24
  • 通讯作者: *hui.wei@ibms.pumc.edu.cn
  • 基金资助:
    国家自然科学基金面上项目(82071504)

Venlafaxine stabilizes axons of the neurons in depression model mice

SUI Jiaping, WEI Hui*   

  1. State Key Laboratory of Common Mechanism Research for Major Diseases, Institute of Basic Medical Sciences CAMS, School of Basic Medicine PUMC, Beijing 100005, China
  • Received:2024-03-06 Revised:2024-04-24 Online:2024-06-05 Published:2024-05-24
  • Contact: *hui.wei@ibms.pumc.edu.cn

摘要: 目的 探究文拉法辛能否升高锚蛋白G(AnkG)表达从而改善小鼠的抑郁症状。方法Synapsin-Cre1小鼠与Ankyrin3-floxed小鼠互交产生Ank3条件性敲低鼠,将条件性Ank3敲低鼠与同窝野生型小鼠分别分成文拉法辛组和0.9%氯化钠溶液(NS)组,文拉法辛组小鼠每日灌胃1 g/L的文拉法辛溶液,200μL/d,其他组给予等体积的NS,持续4周。利用糖水偏好、Y迷宫等实验对小鼠进行抑郁相关行为学检测。通过Western blot对比了4组小鼠皮质区AnkG及突触后致密区蛋白95(PSD95)表达水平,又进行了多重免疫组化对比了4组小鼠海马区AnkG及微管关联蛋白2(MAP2)水平。 结果与野生-NS组比较,敲低-NS小鼠对糖水的偏好显著下降(P<0.001),同时存在自发轮替率的下降(P<0.05),证明成功模拟了抑郁症患者的快感缺失及认知障碍症状。与敲低-NS组相比,文拉法辛可显著升高Ank3敲低小鼠对糖水的偏爱(P<0.001),提高其自发轮替率(P<0.05),改善认知能力。敲低-文拉法辛组小鼠皮质的AnkG及PSD95含量显著高于敲低-NS组小鼠对应脑区的表达水平(P<0.01)。敲低-文拉法辛组小鼠海马的AnkG及MAP2含量显著高于敲低-NS组小鼠对应脑区的表达水平(P<0.05)。结论 文拉法辛能够改善Ank3敲低引起的抑郁相关症状,文拉法辛治疗抑郁症的机制可能与升高前额叶皮质及海马AnkG水平有关。

关键词: 重型抑郁症, 文拉法辛, 锚蛋白

Abstract: Objective To investigate whether the effects of venlafaxine on major depression disorder is associated with ankyrin G. Methods Breed Synapsin-Cre1 and Ankyrin3-floxed mice (Ank3 cKO mice). Ank3 cKO mice and wild type mice were randomly divided into model and control groups. All mice in model group and control group were orally administrated with venlafaxine(1 g/L) or the solvent(normal saline, NS) with the volume of 200 μL,respectively. Depression-related behaviors were examined by sucrose preference test (SPT) and Y maze test. The level of ankyrin G and PSD95 in the cortex of four groups were detected by Western blot. The level of ankyrin G and MAP2 in the in hippocampus of four groups were detected by immunohistochemistry method. ResultsCompared with wt-saline group, the cKO mice in saline showed a significantly decreased preference of sucrose (P<0.001) and low spontaneous alteration(P<0.05). Compared with cKO control ones, the venlafaxine model cKO mice showed remarkably increased preference of sucrose(P<0.001) and more spontaneous alteration(P<0.05). The level of ankyrin G and PSD-95 in the cortex of venlafaxine cKO mice was much higher than that in control mice(P<0.01)The level of ankyrin G and MAP2 in the hippocampus of venlafaxine cKO mice were much higher than those of control mice(P<0.05). Conclusions Venlafaxine alleviates the depression symptoms caused by knocking down Ank3. The mechanism of depression treatment by venlafaxine is potentially associated with levitating ankyrin G level in prefrontal cortex and hippocampus.

Key words: major depression disorder, venlafaxine, ankyrin

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