海马小胶质细胞在小鼠慢性炎性痛所致负性情绪中的形态变化

李威 刘志文 曾佳玉 曾学晴 袁婧 钟小林 万炜

解剖学报 ›› 2021, Vol. 52 ›› Issue (3) : 352-357.

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解剖学报 ›› 2021, Vol. 52 ›› Issue (3) : 352-357. DOI: 10.16098/j.issn.0529-1356.2021.03.004
神经生物学

海马小胶质细胞在小鼠慢性炎性痛所致负性情绪中的形态变化

  • 李威刘志文曾佳玉曾学晴袁婧钟小林3* 万炜1,4*
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Relationship between complete Freund’s adjuvant-induced chronic pain-induced negative emotions and morphological changes of hippocampal microglia

  • LI Wei1  LIU Zhi-wen ZENG Jia-yu1  ZENG Xu-qing YUAN Jing1  ZHONG Xiao-lin3*  WAN Wei1,4*
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摘要

目的  探讨完全弗氏佐剂(CFA)所致慢性炎性痛小鼠模型情绪及海马小胶质细胞形态的改变。   方法  32只ICR雄性小鼠随机分成生理盐水对照组(NS)和完全弗氏佐剂组(CFA)。右后爪足底注射CFA建立小鼠慢性炎性痛模型。采用Von Frey纤维针测量小鼠右足底注射CFA后机械痛阈的变化;采用旷场实验检测小鼠活动度和焦虑样行为;采用糖水偏好和被迫游泳实验检测小鼠抑郁样行为;采用免疫组织化学法检测小鼠海马小胶质细胞标记物离子钙接头蛋白抗原(IBA-1)的表达;采用Sholl分析方法分析海马齿状回区小胶质细胞形态变化。   结果  小鼠痛阈评分结果显示,与NS组相比,CFA组小鼠机械痛阈明显下降(P<0.05)。行为学结果显示,与NS组相比,CFA组小鼠旷场中央格停留时间减少(P<0.01),糖水偏好百分比下降(P<0.01),被迫游泳实验不动时间增加(P<0.001)。免疫组织化学结果显示,与NS组相比,CFA组小鼠海马齿状回区小胶质细胞数目明显增多(P<0.001)。Sholl分析结果显示,与NS组相比,CFA组小鼠海马齿状回区小胶质细胞交点数目减少(P<0.05)。   结论  在CFA诱导的慢性炎性痛模型中,小鼠的负性情绪可能与海马小胶质细胞形态改变有关。

Abstract

Objective  To investigate the alteration of mood and hippocampal microglia morphology in a mouse model of chronic inflammatory pain induced by complete Freund’s adjuvant (CFA).    Methods  Thirty-two male ICR mice were randomly divided into two groups, including normal saline control group (NS) and CFA model group (CFA). The pain model was established by right hindpaw intraplantar CFA injection. The change of mechanical pain threshold after CFA injection was measured by von Frey fiber needle, the locomotor activity and anxiety-like behavior were determined by open field test (OFT), the depression-like behavior was determined by sucrose preference test (SPT) and forced swimming test (FST). The expression of microglia marker ionized calcium binding adaptor molecule-1 (IBA-1) in the hippocampus was determined by immunohistochemistry and its morphological change was analyzed by Sholl analysis.   Results  Compared with the NS group, the mechanical pain threshold of CFA group decreased significantly (P<0.01). The behavior result  showed that the CFA group showed remarkably reduced time in the inner area (P<0.01) compared with the NS group in the open field test;In the sucrose preference test, the percentage of sucrose preference (P<0.01) of CFA mice decreased significantly compared with the NS mice, while the immobility time of CFA mice (P<0.01) increased significantly in the forced swimming test compared with the NS mice. The immunohistochemistry showed that the number of microglia in the dentate gyrus (DG) of CFA mice increased significantly compared with the NS mice. The Sholl analysis result  showed that compared with the NS mice, the number of intersections of microglia in hippocampal DG decreased significantly in CFA mice.   Conclusion  Our finding  indicates that the negative emotions in CFA-induced chronic inflammatory pain may be related to the morphological changes of hippocampal microglia in the mice.

关键词

完全弗氏佐剂 / 海马 / 小胶质细胞 / 慢性炎性痛 / 负性情绪 / 免疫组织化学 / 小鼠

Key words

Complete Freund’s adjuvant / Hippocampus / Microglia / Chronic inflammatory pain / Negative emotion / Immunohistochemistry / Mouse

引用本文

导出引用
李威 刘志文 曾佳玉 曾学晴 袁婧 钟小林 万炜. 海马小胶质细胞在小鼠慢性炎性痛所致负性情绪中的形态变化[J]. 解剖学报. 2021, 52(3): 352-357 https://doi.org/10.16098/j.issn.0529-1356.2021.03.004
LI Wei LIU Zhi-wen ZENG Jia-yu ZENG Xu-qing YUAN Jing ZHONG Xiao-lin WAN Wei. Relationship between complete Freund’s adjuvant-induced chronic pain-induced negative emotions and morphological changes of hippocampal microglia[J]. Acta Anatomica Sinica. 2021, 52(3): 352-357 https://doi.org/10.16098/j.issn.0529-1356.2021.03.004
中图分类号: R322.81   

参考文献

[1] Zhu C, Xu Q, Mao Z, et al. The chinese medicine Wu-Tou decoction relieves neuropathic pain by inhibiting hippocampal microglia activation[J]. Sci Rep, 2018,8(1)12292.
[2] Ji R, Nackley A, Huh Y, et al. Neuroinflammation and central sensitization in chronic and widespread pain[J]. Anesthesiology, 2018,129(2): 343-366.
[3] Kuner R, Flor H. Structural plasticity and reorganisation in chronic pain[J]. Nat Rev Neurosci, 2017,18(1): 20-30.
[4] Marshall PWM, Schabrun S, Knox MF. Physical activity and the mediating effect of fear, depression, anxiety, and catastrophizing on pain related disability in people with chronic low back pain[J]. PLoS One, 2017, 12(7): e180788.
[5] Ai Amin HA, Atweh SF, Jabbur SJ, et al. Effects of ventral hippocampal lesion on thermal and mechanical nociception in neonates and adult rats[J]. Eur J Neurosci, 2004,20(11): 3027-3034.
[6] Liu Y, Zhou L, Wang J, et al. TNF-α differentially regulates synaptic plasticity in the hippocampus and spinal cord by microglia-dependent mechanisms after peripheral nerve injury[J]. J Neurosci, 2017,37(4): 871-881.
[7] Salter MW, Stevens B. Microglia emerge as central players in brain disease[J]. Nat Med, 2017,23(9): 1018-1027.
[8] Zanier ER, Pischiutta F, Riganti L, et al. Bone marrow mesenchymal stromal cells drive protective M2 microglia polarization after brain trauma[J]. Neurotherapeutics, 2014,11(3): 679-695.
[9] Vogel DY, Vereyken EJ, Glim JE, et al. Macrophages in inflammatory multiple sclerosis lesions have an intermediate activation status[J]. J Neuroinflamm, 2013,10(1): 35.
[10] Kim CC, Nakamura MC, Hsieh CL. Brain trauma elicits non-canonical macrophage activation states[J]. J Neuroinflamm, 2016,13(1):117.
[11] Nimmerjahn A. Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo[J]. Science, 2005,308(5726): 1314-1318.
[12] Kozlowski C, Weimer RM. An automated method to quantify microglia morphology and application to monitor activation state longitudinally in vivo[J]. PLoS One, 2012,7(2): e31814.
[13] Behr MAAM. Freund’s adjuvant, NOD2 and mycobacteria[J]. Curr Opin Microbiol, 2015,23: 126-132.
[14] Shao CJ, Gao Y, Zhao L, et al. Co-application of lidocaine and QX-572 induces divergent pain behaviours in mice[J]. J Pharm Pharmacol, 2015,67(9): 1272-1278.
[15] Luo C, Zhong X, Zhou FH, et al. Peripheral brain derived neurotrophic factor precursor regulates pain as an inflammatory mediator[J]. Sci Rep, 2016,6:27171.
[16] Zeng JY, Wang Zh, Niu L, et al. Effect of Panax notoginseng total saponin on lipopolysaccharide induced depression-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.
[17] 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.
[18] Zhong X, Cao W, Zhao H, et al. MicroRNA-32-5p knockout eliminates lipopolysaccharide-induced depressive-like behavior in mice through inhibition of astrocyte overactivity[J]. Brain Behav Immun, 2020,84: 10-22.
[19] 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.
[20] Abbink MR, Kotah JM, Hoeijmakers L, et al. Characterization of astrocytes throughout life in wildtype and APP/PS1 mice after early-life stress exposure[J]. J Neuroinflamm, 2020,17(1):91.
[21] Chang MC. Conservative treatments frequently used for chronic pain patients in clinical practice: a literature review[J]. Cureus, 2020,8(12): e9934.
[22] Liao HY, Hsieh CL, Huang CP, et al. Electroacupuncture attenuates CFA-induced inflammatory pain by suppressing Nav1. 8 through S100B, TRPV1, opioid, and adenosine pathways in mice[J]. Sci Rep, 2017,7: 42531.
[23] Yang Y, Wang Z, Jin S, et al. Opposite monosynaptic scaling of BLP-vCA1 inputs governs hopefulness-and helplessness-modulated spatial learning and memory[J]. Nat Commun, 2016,7:11935.
[24] Binley KE, Ng WS, Tribble JR, et al. Sholl analysis: a quantitative comparison of semi-automated methods[J]. J Neurosci Methods, 2014,225: 65-70.
[25] Garcia-Segura LM, Perez-Marquez J. A new mathematica function to evaluate neuronal morphology using the Sholl analysis[J]. J Neurosci Methods, 2014, 226: 103-109.

基金

湖南省自然科学基金省市联合项目;湖南省自然科学基金青年项目;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

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