解剖学报 ›› 2021, Vol. 52 ›› Issue (5): 686-691.doi: 10.16098/j.issn.0529-1356.2021.05.003

• 神经生物学 • 上一篇    下一篇

自主跑轮运动通过促进海马神经发生改善甲醛所致小鼠的负性情绪

李威1 周鑫1 谢志艳1 张天乐1 杨惠2 曹文宇1 刘志文3* 曾佳玉1*   

  1. 1.南华大学衡阳医学院应用解剖学与生殖医学研究所,湖南 衡阳 421001; 2.南华大学附属第一医院病理科,湖南 衡阳 421001; 3.南华大学附属第二医院麻醉科,湖南 衡阳 421001
  • 收稿日期:2019-11-27 修回日期:2020-02-15 出版日期:2021-10-06 发布日期:2021-10-06
  • 通讯作者: 刘志文;曾佳玉 E-mail:1242461483@qq.com
  • 基金资助:
    湖南省教育厅优秀青年项目;南华大学大学生研究性学习和创新性实验计划项目;南华大学大学生研究性学习和创新性实验计划项目;南华大学大学生研究性学习和创新性实验计划项目

Voluntary wheel running prevents the formaldehyde induced negativeemotion through up-regulation of hippocampal neurogenesis in mice#br#

LI Wei1 ZHOU Xin1 XIE Zhi-yan1 ZHANG Tian-le1 YANG Hui2 CAO Wen-yu1 LIU Zhi-wen3*  ZENG Jia-yu1*   

  1. 1.Clinical Anatomy and Reproductive Medicine Application Institute, School of Medicine, University of South China, Hu’nan Hengyang 421001, China; 2.Department of Clinical Pathology, the First Affiliated Hospital of University of South China, Hu’nan Hengyang 421001, China;  3.Department of Clinical Anesthesiology, the Second Affiliated Hospital of University of South China, Hu’nan Hengyang 421001, China
  • Received:2019-11-27 Revised:2020-02-15 Online:2021-10-06 Published:2021-10-06
  • Contact: LIU Zhi-wen;ZENG Jia-yu E-mail:1242461483@qq.com

摘要:

目的  探讨自主跑轮运动对甲醛疼痛模型小鼠负性情绪的影响。   方法  30只昆明雄鼠随机分成生理盐水对照组(NS)、甲醛组(F)、自主跑轮运动+甲醛组(R+F)。右后爪足底皮下注射0.4%甲醛建立疼痛模型,R+F组在模型建立之前置于小鼠跑轮运动装置3周。以实验小鼠舔足累计时间评价自发痛行为;采用旷场实验(OFT)和高架十字迷宫实验(EPM)检测小鼠焦虑样行为;采用被迫游泳实验(FST)检测小鼠抑郁样行为;采用免疫组织化学方法检测海马未成熟神经元标记物双皮层蛋白(DCX)的表达情况。   结果  自发痛评分结果显示,与NS组相比,F组小鼠出现典型的双相痛反应,与F组相比, R+F组小鼠的第Ⅱ相时段舔咬足累计时间明显缩短(P<0.01)。旷场实验结果显示,与NS组相比,F组小鼠在中央格探索时间显著减少(P<0.001),与F组相比,R+F组小鼠在中央格探索的时间增加(P<0.05)。高架十字迷宫实验结果显示,与NS组相比,F组小鼠进入开放臂的时间显著减少(P<0.001),与F组相比,R+F组小鼠进入开放臂的时间增加(P<0.05)。被迫游泳实验结果显示,与NS组相比,F组小鼠不动时间明显增加(P<0.01),与F组相比,R+F组小鼠不动时间缩短(P<0.05)。免疫组织化学结果显示,与NS组(250.90±16.22)相比,F组小鼠海马DCX阳性细胞面积(210.90±7.98)减少,与F组相比,R+F组小鼠海马DCX阳性细胞面积显著增多(284.00±9.84)。   结论  自主跑轮运动可能通过促进海马神经发生,从而改善甲醛所致小鼠的自发痛与焦虑、抑郁样行为。

关键词: 自主跑轮运动, 神经发生, 焦虑样行为, 抑郁样行为, 甲醛, 疼痛, 免疫组织化学, 小鼠

Abstract:

Objective  To investigate the effect of voluntary wheel running on negative affective of mice induced by formaldehyde.    Methods  Thirty male Kunming mice were randomly divided into three groups, including normal saline control group (NS), formaldehyde model group (F), and voluntary wheel running with formaldehyde injection group (R+F). The pain model was established by right hindpaw intraplantar formalin injection, the mice of R+F group experienced voluntary wheel running for three weeks before intraplantar formaldehyde injection. The spontaneous pain behavior was determined by the cumulative time of licking paw. The anxiety-like behavior of each group was determined by open field test (OFT) and elevated plus-maze test (EPM) while the depression-like behavior of each group was determined by forced swimming test (FST). The expression of doublecortin(DCX)in the hippocampus was determined by immunohistochemistry.    Results  Compared with the NS group, the typical two-phase pain response was observed in the F group, and compared with the F group,the second phase pain duration was significantly reduced in the R+F group (P<0.01).  In the open field test, the F group showed remarkably reduced time in the inner area(P<0.001) compared with the NS group, while the R+F group increased time in the inner area (P<0.05) compared with the F group. In the elevated plus-maze test, the F group showed remarkably reduced time (P<0.001)spent in the open arm compared with the NS group,however,compared with the F group, R+F group increased time spent in the open arm (P<0.05). In the forced swimming test, the immobility time of the F group significant increased (P<0.01) compared with the NS group, which was decreased in the R+F group (P<0.05). The Immunohistochemistry showed that the area of DCX positive cells in the hippocampus of the F group was downregulated compared with the NS group, which was upregulated in the R+F group.    Conclusion  Our findings indicate that voluntary wheel running can improve anxiety and depression-like in mice induced by formaldehyde injection, which may be related to enhanced neurogenesis in the hippocampus.

Key words: Voluntary wheel running, Neurogenesis, Anxiety-like behavior, Depression-like behavior, Formalin, Pain, Immunohistochemistry, Mouse

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