创伤后应激障碍小鼠初级体感皮质神经元异常敏化的研究

Abnormal sensitization of primary somatosensory cortex neurons in mice with post-traumatic stress disorder

目的:分析创伤后应激障碍(PTSD)小鼠胡须触觉刺激后初级躯体感觉皮质(S1)神经元的激活情况及PTSD小鼠S1皮质神经元的形态结构变化。方法:使用神经元细胞骨架相关蛋白(Arc)标记策略,结合免疫荧光染色技术,对PTSD小鼠与对照组小鼠胡须刺激后S1皮质神经元Arc进行标记并观察,通过分析Arc标记神经元的空间表达位置和阳性细胞数量差异,对比分析两组S1皮质神经元的激活水平。利用病毒稀疏标记方法标记S1皮质的锥体神经元,比较两组小鼠神经元树突数量及树突棘的形态与数量分布。结果:胡须刺激两组小鼠后发现Arc阳性神经元在S1浅层至深层均有分布,其中在Ⅱ/Ⅲ与Ⅴ层分布更密集。与对照组小鼠相比,PTSD组在不同层的阳性神经元数目均明显增多。细胞形态结构分析结果显示,与对照组神经元相比,PTSD组小鼠树突棘密度在Ⅱ/Ⅲ层异常增高,其中蘑菇型树突棘数量增多,丝状伪足型树突棘数量减少;而S1Ⅴ层蘑菇型与细长型的树突棘数量均较多,但树突棘总数没有明显差异。结论:PTSD小鼠胡须刺激后S1神经元过度激活,神经元结构及形态发生明显改变。

Objective:To analyze the activation of primary somatosensory cortex(S1)neurons in post-traumatic stress disorder(PTSD)mice after tactile stimulation of whiskers and the changes of S1 cortical neurons in PTSD mice.Methods:Using the neuron cytoskeleton-associated protein(Arc)labeling strategy and immunofluorescence staining technique,the Arc of S1 cortical neurons in PTSD mice and control mice after whisker stimulation was marked and observed.By analyzing the difference in the spatial expression position of Arc labeled neurons and the number of positive cells,the activation level of S1 cortical neurons in the two groups was compared and analyzed.The pyramidal neurons of S1 cortex were labeled by sparse virus labeling method,and the number of dendrites and the morphology and number distribution of dendritic spines were compared between the two groups.Results:After whisker stimulation,it was found that Arc positive neurons were distributed from shallow layer to deep layer of S1,and more densely distributed in layersⅡ/ⅢandⅤ.Compared with the control group,the number of positive neurons in different layers of the PTSD group was significantly increased.The results of cell morphology and structure analysis showed that,compared with the control group,the density of dendritic spines in layer II/III of mice with PTSD increased,and the number of mushroom dendritic spines increased,while the number of filamentous pseudopod dendritic spines decreased.The number of dendritic spines of S1Ⅴlayer mushroom type and slender type was higher,but the total number of dendritic spines was not significantly different.Conclusion:After whisker stimulation in PTSD mice,S1 neurons were over-activated,and the structure and morphology of neurons changed significantly.