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文拉法辛提升抑郁模型小鼠的神经元轴突结构稳定性OACSTPCD

Venlafaxine stabilizes axons of the neurons in depression model mice

中文摘要英文摘要

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 将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 1g/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.

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.Results Compared 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 levita-ting ankyrin G level in prefrontal cortex and hippocampus.

隋家平;韦晖

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

临床医学

重型抑郁症文拉法辛锚蛋白

major depression disordervenlafaxineankyrin

《基础医学与临床》 2024 (006)

809-815 / 7

国家自然科学基金面上项目(82071504)

10.16352/j.issn.1001-6325.2024.06.0809

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