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 周鑫 谢志艳 张天乐 杨惠 曹文宇 刘志文 曾佳玉

解剖学报 ›› 2021, Vol. 52 ›› Issue (5) : 686-691.

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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

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*
作者信息 +

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*
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文章历史 +

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。

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.

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

Key words

Voluntary wheel running / Neurogenesis / Anxiety-like behavior / Depression-like behavior / Formalin / Pain / Immunohistochemistry / Mouse

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导出引用
李威 周鑫 谢志艳 张天乐 杨惠 曹文宇 刘志文 曾佳玉. 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[J]. 解剖学报. 2021, 52(5): 686-691 https://doi.org/10.16098/j.issn.0529-1356.2021.05.003
LI Wei ZHOU Xin XIE Zhi-yan ZHANG Tian-le YANG Hui CAO Wen-yu LIU Zhi-wen ZENG Jia-yu. Voluntary wheel running prevents the formaldehyde induced negativeemotion through up-regulation of hippocampal neurogenesis in mice#br#[J]. Acta Anatomica Sinica. 2021, 52(5): 686-691 https://doi.org/10.16098/j.issn.0529-1356.2021.05.003
中图分类号: R322.81   

参考文献

[1] Khoutorsky A, Price TJ. Translational control mechanisms in persistent pain[J]. Trends Neurosci, 2018, 41(2):100-114.
[2] Albrecht DS, Kim M, Akeju O, et al. The neuroinflammatory component of negative affect in patients with chronic pain [J]. Mol Psychiatry, 2021,26(3):864-874..
[3] Schmitt A, Martin JA, Rojas S, et al. Effects of low-and high-intensity exercise on emotional face processing: an fMRI face-matching study [J]. Soc Cogn Affect Neurosci, 2019, 14 (6): 657-665.
[4] Droste C, Meyer-Blankenburg H, Greenlee MW, et al. Effect of physical exercise on pain thresholds and plasma beta-endorphins in patients with silent and symptomatic myocardial ischaemia[J]. Eur Heart J, 1988, 9 (Suppl N):25-33.
[5] Novak CM, Burghardt PR, Levine JA. The use of a running wheel to measure activity in rodents: relationship to energy balance, general activity, and reward [J]. Neurosci Biobehav Rev, 2012, 36(3):1001-1014.
[6] Dahlin E, Andersson M, Thoren A, et al. Effects of physical exercise and stress on hippocampal CA1 and dentate gyrus synaptic transmission and long-term potentiation in adolescent and adult Wistar rats[J]. Neuroscience, 2019,408:22-30.
[7] Andoh M, Shibata K, Okamoto K, et al. Exercise reverses behavioral and synaptic abnormalities after maternal inflammation [J]. Cell Rep, 2019, 27(10):2817-2825.
[8] Vetreno RP, Lawrimore CJ, Rowsey PJ, et al. Persistent adult neuroimmune activation and loss of hippocampal neurogenesis following adolescent ethanol exposure: blockade by exercise and the anti-inflammatory drug indomethacin[J]. Front Neurosci, 2018,12:200.
[9] Littlefield AM, Settis E, Priester C, et al. Voluntary exercise attenuates LPS-induced reductions in neurogenesis and increases microglia expression of a proneurogenic phenotype in aged mice[J]. J Neuroinflammation, 2015,12:138.
[10] O’leary JD, Hoban AE, Murphy A, et al. Differential effects of adolescent and adult-initiated exercise on cognition and hippocampal neurogenesis[J]. Hippocampus, 2019, 29(4): 352-365.
[11] Romero-Grimaldi C, Berrocoso E, Alba-Delgado C, et al. Stress increases the negative effects of chronic pain on hippocampal neurogenesis [J]. Anesth Analg, 2015,121(4): 1078-1088.
[12] Hunskaar S, Fasmer OB, Hole K. Formalin test in mice, a useful technique for evaluating mild analgesics [J]. J Neurosci Methods, 1985, 14(1):69-76.
[13] Zhong XL, Wei R, Zhou P, et al. Activation of anterior cingulate cortex extracellular signal-regulated kinase-1 and-2 (ERK1/2) regulates acetic acid-induced, pain-related anxiety in adult female mice[J]. Acta Histochem Cytochem, 2012,45(4):219-225.
[14] Xu Y, Cao W, Zhou M, et al. Inactivation of BRD7 results in impaired cognitive behavior and reduced synaptic plasticity of the medial prefrontal cortex[J]. Behav Brain Res, 2015,286:1-10.
[15] Zeng JY, Wang Zh, Niu L, et al.Effect of Panax notoginseng total saponin on lipopolysaccharide induceddepression-like behavior and expression of microglia in mice [J]. Acta Anatomica Sinica, 2018,49(2):166-171. (in Chinese)
曾佳玉, 王贞, 牛磊, 等.三七总皂苷对脂多糖诱导小鼠抑郁样行为及脑内小胶质细胞表达的影响[J]. 解剖学报, 2018,49(2):166-171.
[16] Mcglone F, Reilly D. The cutaneous sensory system [J]. Neurosci Biobehav Rev, 2010, 34(2):148-159.
[17] Auvray M, Myin E, Spence C. The sensory-discriminative and affective-motivational aspects of pain [J]. Neurosci Biobehav Rev, 2010, 34(2):214-223.
[18] Okuda K, Sakurada C, Takahashi M, et al. Characterization of nociceptive responses and spinal releases of nitric oxide metabolites and glutamate evoked by different concentrations of formalin in rats[J]. Pain, 2001, 92(1-2):107-115.
[19] Luo C, Zhang YL, Luo W, et al. Differential effects of general anesthetics on anxiety-like behavior in formalin-induced pain: involvement of ERK activation in the anterior cingulate cortex[J]. Psychopharmacology (Berl), 2015, 232(24):4433-4444.
[20] Wang Zh, Huang YJ, Nai AT, et al. Fluoxetine improving the depression-like behavior induced by chronic restraint stress by up-regulation the expression of bromodomaincontaining protein 4 in hippocampus of mouse[J]. Acta Anatomica Sinica, 2019,50(1):18-23. (in Chinese)
王贞, 黄怡佳, 乃爱桃, 等.氟西汀通过上调海马内溴结构域蛋白4的表达改善慢性束缚应激所致小鼠的抑郁样行为[J]. 解剖学报, 2019,50(1):18-23.
[21] Fasick Ⅴ, Spengler RN, Samankan S, et al. The hippocampus and TNF: common links between chronic pain and depression [J]. Neurosci Biobehav Rev, 2015,53:139-159.
[22] Kheirbek MA, Klemenhagen KC, Sahay A, et al. Neurogenesis and generalization: a new approach to stratify and treat anxiety disorders [J]. Nat Neurosci, 2012,15(12):1613-1620.
[23] Snyder JS, Soumier A, Brewer M, et al. Adult hippocampal neurogenesis buffers stress responses and depressive behaviour [J]. Nature, 2011, 476(7361):458-461.
[24] Morgan JA, Singhal G, Corrigan F, et al. The effects of aerobic exercise on depression-like, anxiety-like, and cognition-like behaviours over the healthy adult lifespan of C57BL/6 mice [J]. Behav Brain Res, 2018,337:193-203.
[25] Huang YQ, Wu C, He XF, et al. Effects of voluntary wheel-running types on hippocampal neurogenesis and spatial cognition in middle-aged mice[J]. Front Cell Neurosci, 2018,12:177.

基金

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

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