文拉法辛提升抑郁模型小鼠的神经元轴突结构稳定性  

Venlafaxine stabilizes axons of the neurons in depression model mice

作　　者：隋家平 韦晖 SUI Jiaping;WEI Hui(State Key Laboratory of Common Mechanism Research for Major Diseases,Institute of Basic Medical Sciences CAMS,School of Basic Medicine PUMC,Beijing 100005,China)

机构地区：[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

出　　处：《基础医学与临床》2024年第6期809-815,共7页Basic and Clinical Medicine

基　　金：国家自然科学基金面上项目(82071504)。

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。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 200μL,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 levitating ankyrin G level in prefrontal cortex and hippocampus.

关 键 词：重型抑郁症 文拉法辛 锚蛋白 

分 类 号：R749.053[医药卫生—神经病学与精神病学]