运动促进海马神经再生与树突发育缓解创伤后应激障碍小鼠的恐惧与焦虑

苏畅  许子萱  金硕 张晓晓  席超  孙丽娜

doi:10.16098/j.issn.0529-1356.2025.04.002

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解剖学报 ›› 2025, Vol. 56 ›› Issue (4) : 389-397. DOI: 10.16098/j.issn.0529-1356.2025.04.002

神经生物学

运动促进海马神经再生与树突发育缓解创伤后应激障碍小鼠的恐惧与焦虑

苏畅¹ 许子萱¹ 金硕¹张晓晓¹席超^2* 孙丽娜^1,3*

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Exercise alleviating fear and anxiety in mice with post-traumatic stress disorder by promoting hippocampal neuroregeneration and dendritic development

SU Chang¹ XU Zi-xuan¹ JIN Shuo¹ ZHANG Xiao-xiao¹ XI Chao^2* SUN Li-na^1,3*

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摘要

目的探讨改善创伤后应激障碍(PTSD)恐惧与焦虑症状的海马新生神经元可塑性机制。方法将40只C57BL/6J雄性小鼠随机分为对照组(Ctrl)和PTSD组，其中PTSD组分为不运动组(PTSD)、低强度运动组(L)和高强度运动组(H)。使用条件性足部电击(CF)和单次-持续应激(SPS)结合的方式构建小鼠PTSD模型；利用条件性恐惧实验和高架十字迷宫实验评估小鼠的恐惧和焦虑水平；通过免疫荧光双标染色检测海马齿状回（DG）区新生成熟神经元密度，并在海马DG区注射逆转录病毒pRetro-U6-EF1-EGFP-3xFLAG-WPRE和观察新生神经元的树突长度与分支点数量；采用ELISA测定海马脂联素 (APN)浓度。结果高、低强度的运动干预均能使PTSD小鼠在条件性恐惧测试中的不动时间明显减少；高强度组小鼠在高架十字迷宫开放臂的停留时间及进入次数较PTSD组显著增加，在闭合臂的停留时间及进入次数明显减少。此外，高强度组小鼠的海马DG区新生成熟神经元密度、树突长度、树突分支点数量均显著增加。高、低强度组小鼠海马APN浓度较PTSD组显著升高，且高强度组更明显。结论运动能改善PTSD小鼠的恐惧和焦虑症状，并提高PTSD小鼠的海马神经可塑性和APN分泌，提示运动改善PTSD的恐惧和焦虑症状可能与APN分泌增加所介导的海马神经可塑性增强有关，且改善效果与运动强度成正相关，即高强度运动改善效果更好。

Abstract

Objective To investigate the mechanism of hippocampal neuronal plasticity of newborn neurons in the hippocampus by which exercise improves the fear and anxiety symptoms of post-traumatic stress disorder (PTSD). Methods Totally 40 C57BL/6J male mice were randomly divided into by control group (Ctrl) and PTSD group, the PTSD group was divided into a no-exercise group (PTSD), a low-intensity exercise group (L) and a high-intensity exercise group (H). The PTSD model mice were constructed by combining conditioned plantar-foot shock (CF) and single-session sustained stress (SPS). After the exercise intervention, the fear and anxiety levels of the mice were assessed using the conditioned fear test and the elevated cross maze test; Subsequently, the densities of the newborn mature neurons in dentate gyrus(DG) of hippocampus were detected by immunofluorescent double-labelling staining, and the newborn neuron morphology was marked by injecting retrovirus pRetro-U6-EF1-EGFP-3xFLAG-WPRE in DG of hippocampus to observe its morphology. The morphology of the newborn neurons was labelled to observe their dendritic length and the number of branch points; Meanwhile, the concentration level of adiponctin(APN) in the hippocampal area was determined by ELISA. Results The result showed that both high and low-intensity exercise interventions significantly reduced the freezing time of PTSD mice in the conditioned fear test, and in the elevated cross maze experiment, the residence time and the number of entries in the open arm of the mice in the H group increased significantly compared with those in the PTSD group, while the residence time and the number of entries in the closed arm were significantly reduced. In addition, both high and low-intensity exercise interventions significantly increased the surface density and dendritic length of newborn mature neurons in the hippocampal DG region of PTSD mice, and high-intensity exercise significantly increased the number of dendritic branching points, and the density of newborn mature neurons in the H group was more significantly increased compared with that in the L group. At the same time, the hippocampal APN concentration increased significantly in both L and H groups compared with the PTSD group, and it was more significant in the H group. Conclusion Exercises have an ameliorative effect on anxiety and fear symptoms in PTSD mice, and at the same time, it can increase hippocampal neuroplasticity and adiponctin secretion in PTSD mice, suggesting that the improvement of fear and anxiety symptoms in PTSD by exercise may be related to the increase of hippocampal neuroplasticity and APN secretion, and the improvement effect is better with high-intensity exercise.

关键词

创伤后应激障碍 / 运动 / 海马神经再生 / 树突发育 / 神经可塑性 / 免疫荧光 / 小鼠

Key words

Post-traumatic stress disorder

/ Exercise / Hippocampal neurogenesis / Dendritic development / Neuroplasticity / Immunofluorescence / Mouse

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苏畅许子萱金硕张晓晓席超孙丽娜. 运动促进海马神经再生与树突发育缓解创伤后应激障碍小鼠的恐惧与焦虑[J]. 解剖学报. 2025, 56(4): 389-397 https://doi.org/10.16098/j.issn.0529-1356.2025.04.002

SU Chang XU Zi-xuan JIN Shuo ZHANG Xiao-xiao XI Chao SUN Li-na.

Exercise alleviating fear and anxiety in mice with post-traumatic stress disorder by promoting hippocampal neuroregeneration and dendritic development

[J]. Acta Anatomica Sinica. 2025, 56(4): 389-397 https://doi.org/10.16098/j.issn.0529-1356.2025.04.002

中图分类号： R395.4 R455 R749

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