跑步对抑郁大鼠内侧前额叶皮质兴奋性突触的影响

Effects of running on excitatory synapses in medial prefrontal cortex in rat model of depression

摘要

目的 精确定量研究跑步锻炼对慢性束缚应激（chronic restraint stress，CRS）诱导的抑郁模型大鼠内侧前额叶皮质（medial prefrontal cortex，mPFC）内Sp⁺兴奋性突触数量的影响。 方法 选取雄性SD大鼠（54只），经过适应性喂养和糖水基线调整，在CRS模型建立成功后随机分为对照组、抑郁模型组和模型跑步组，其中模型跑步组大鼠在束缚的第5周开始进行为期4周的跑步锻炼干预。最后，对各组大鼠进行行为学测试，并运用免疫组织化学技术结合现代体视学方法对各组大鼠mPFC内Sp⁺兴奋性突触变化进行精确定量研究。 结果 与对照组［（97.14±2.64）%］相比，抑郁模型组和模型跑步组大鼠糖精偏好百分比［（89.62±6.05）%］减少（P=0.002），体质量的增长减缓，强迫游泳实验中大鼠的不动时间和新环境进食抑制实验的进食潜伏期增加。4周的跑步锻炼可以有效减缓抑郁模型组大鼠糖精偏好百分比的下降［（89.30±5.06）% vs. （97.30±2.08）%，P=0.018］，降低强迫游泳实验中抑郁大鼠的不动时间，并在新环境进食抑制实验中缩短抑郁大鼠的进食潜伏期。体视学精确定量分析结果显示，抑郁模型组大鼠mPFC内的Sp⁺兴奋性突触总量［（9.98±0.35）×10⁸个］低于对照组［（11.50±1.27）×10⁸个，P=0.013］。而跑步锻炼则可以逆转抑郁大鼠mPFC内的Sp⁺兴奋性突触总数的减少［模型跑步组（11.30±1.21）×10⁸个，P=0.003］。 结论 跑步锻炼干预后CRS抑郁模型大鼠mPFC的Sp⁺兴奋性突触数量的改变可能是跑步锻炼发挥抗抑郁作用的神经生物学基础之一。

Abstract

Objective To precisely and quantitatively study the effects of running exercise on the number of spinophilin（Sp⁺） excitatory synapses in the medial prefrontal cortex（mPFC） in a rat model of depression induced by chronic restraint stress（CRS）. Methods After adaptive feeding and baseline saccharin preference testing，54 male Sprague-Dawley rats were randomly divided into three groups：control group，CRS depression model group，and model+running group. The model+running group had 4-week running exercise since the 5th week of restraint. Then behavioral tests were performed for each group. The changes in Sp⁺ excitatory synapses in mPFC were measured quantitatively and precisely by immunohistochemistry and modern stereology. Results Compared with the control group，the depression model group showed a significantly lower saccharin preference［（97.14±2.64）% vs. （89.62±6.05）%，P=0.002］，a significantly slower increase in body weight，a significantly longer immobility time in the forced swimming test，and a significantly longer latency to eat in the novelty-suppressed feeding test. Compared with the depression model group，4-week running significantly increased saccharin preference［（89.30±5.06）% vs. （97.30±2.08）%，P=0.018］，and significantly shortened the immobility time of the forced swimming test and the latency to eat in the novelty-suppressed feeding test. The stereology results revealed a significantly less total number of Sp⁺ excitatory synapses in mPFC in the depression model group than in the control group ［（9.98±0.35）×10⁸ vs. （11.50±1.27）×10⁸，P=0.013］；and running exercise significantly reversed the decrease in the total number of Sp⁺ excitatory synapses in mPFC in depressive rats［（11.30±1.21）×10⁸，P=0.003］. Conclusion Modulating the number of Sp⁺ excitatory synapses in mPFC may be one of the neurobiological bases for running to relieve depression.

关键词

跑步锻炼 / 抑郁症 / 兴奋性突触 / 内侧前额叶皮质 / 体视学

Key words

running exercise / depression / excitatory synapse / medial prefrontal cortex / stereology

基金资助

国家自然科学基金青年基金资助项目(81501156)