Exercise more efficiently regulates the maturation of newborn neurons and synaptic plasticity than fluoxetine in a CUS-induced depression mouse model
Exercise more efficiently regulates the maturation of newborn neurons and synaptic plasticity than fluoxetine in a CUS-induced depression mouse model
复制标题
在 CUS 诱导的抑郁小鼠模型中，运动比氟西汀更有效地调节新生神经元的成熟和突触可塑性
DOI：
10.1016/j.expneurol.2022.114103
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发表时间：
2022-05-18
影响因子：
5.3
通讯作者：
Tang, Yong
中科院分区：
文献类型：
--
作者：
Liang, Xin;Tang, Jing;Tang, Yong
抑郁症是世界范围内发病率和死亡率的一个常见和重要原因，通常采用抗抑郁药、电击和心理疗法进行治疗。最近，越来越多的证据表明，运动可以有效缓解抑郁症。为探讨运动与经典抗抑郁药氟西汀治疗抑郁症的疗效差异，我们设立了4组：对照组、慢性不可预见性应激（CUS/STD）组、跑步（CUS/RUN）组和氟西汀（CUS/FLX）组。采用蔗糖偏好试验（SPT）、强迫游泳试验（FST）、悬尾试验（TST）、免疫组化、免疫荧光和体视学分析等方法，探讨运动与氟西汀治疗抑郁症的疗效差异及其机制。在第7周，CUS/RUN组的蔗糖偏好显著高于CUS/STD组，而CUS/FLX组的蔗糖偏好直到第8周才与CUS/STD组差异无显著性。运动减少了FST和TST中的不动时间，而氟西汀仅减少了TST中的不动时间。海马结构分析显示，CUS/STD组未成熟神经元增多，成熟神经元减少。运动减少了未成熟神经元的数量，增加了成熟神经元的数量，但氟西汀治疗后没有观察到成熟神经元的数量增加。此外，跑步和百忧解都可以逆转抑郁小鼠MAP 2+树突数量的减少。运动增加了海马CA1，CA3和齿状回（DG）区域的spinophilin阳性（SP+）树突棘的数量，而氟西汀只增加了DG中SP+棘的数量。总之，运动促进DG中的新生神经元成熟，并调节海马三个亚区的神经元可塑性，这可能解释了为什么跑步比氟西汀更早和更全面地发挥抗抑郁作用。
Depression, a common and important cause of morbidity and mortality worldwide, is commonly treated with antidepressants, electric shock and psychotherapy. Recently, increasing evidence has shown that exercise can effectively alleviate depression. To determine the difference in efficacy between exercise and the classic antidepressant fluoxetine in treating depression, we established four groups: the Control, chronic unpredictable stress (CUS/STD), running (CUS/RUN) and fluoxetine (CUS/FLX) groups. The sucrose preference test (SPT), the forced swimming test (FST), the tail suspension test (TST), immunohistochemistry, immunofluorescence and stereological analyses were used to clarify the difference in therapeutic efficacy and mechanism between exercise and fluoxetine in the treatment of depression. In the seventh week, the sucrose preference of the CUS/RUN group was significantly higher than that of the CUS/STD group, while the sucrose preference of the CUS/FLX group did not differ from that of the CUS/STD group until the eighth week. Exercise reduced the immobility time in the FST and TST, while fluoxetine only reduced immobility time in the TST. Hippocampal structure analysis showed that the CUS/STD group exhibited an increase in immature neurons and a decrease in mature neurons. Exercise reduced the number of immature neurons and increased the number of mature neurons, but no increase in the number of mature neurons was observed after fluoxetine treatment. In addition, both running and fluoxetine reversed the decrease in the number of MAP2+ dendrites in depressed mice. Exercise increased the number of spinophilin-positive (Sp+) dendritic spines in the hippocampal CA1, CA3, and dentate gyrus (DG) regions, whereas fluoxetine only increased the number of SP+ spines in the DG. In summary, exercise promoted newborn neuron maturation in the DG and regulated neuronal plasticity in three hippocampal subregions, which might explain why running exerts earlier and more comprehensive antidepressant effects than fluoxetine.