|本期目录/Table of Contents|

[1]岳亮,李坤,庞金卫,等.奥沙利铂化疗对小鼠行为及内侧前额叶皮层中少突胶质细胞前体细胞的影响[J].医学研究与战创伤救治(原医学研究生学报),2025,38(01):1-8.[doi:10.16571/j.cnki.2097-2768.2025.01.001]
　YUE Liang,LI Kun,PANG Jinwei,et al.Effects of oxaliplatin chemotherapy on behavior and oligodendrocyte precursor cells in the medial prefrontalcortex of mice[J].JOURNAL OF MEDICALRESEARCH —COMBAT TRAUMA CARE,2025,38(01):1-8.[doi:10.16571/j.cnki.2097-2768.2025.01.001]
点击复制

奥沙利铂化疗对小鼠行为及内侧前额叶皮层中少突胶质细胞前体细胞的影响()
分享到62.8K

《医学研究与战创伤救治》（原医学研究生学报）[ISSN:1672-271X/CN:32-1713/R]

卷:
38卷
期数:
2025年01期
页码:
1-8
栏目:
论著·基础研究
出版日期:
2025-01-20

文章信息/Info

Title:
Effects of oxaliplatin chemotherapy on behavior and oligodendrocyte precursor cells in the medial prefrontalcortex of mice
文章编号:
2097-2768（2025）01-0001-08
作者:
岳亮; 李坤; 庞金卫; 熊源长
作者单位：200433 上海，海军军医大学第一附属医院疼痛治疗科［岳亮（现在解放军联勤保障部队第九八五医院麻醉科工作）、熊源长］；030001 太原，解放军联勤保障部队第九八五医院麻醉科（李坤、庞金卫）
Author(s):
YUE Liang; LI Kun; PANG Jinwei; XIONG Yuanchang
（1.Department of Pain Management，the First Affiliated Hospital，Naval Medical University，Shanghai 200433，China；2. Department of Anesthesiology，the 985th Hospital of the Joint Logistic Support Force，PLA，Taiyuan 030001，Shanxi，China）
关键词:
奥沙利铂; 抑郁; 内侧前额叶皮层; 少突胶质细胞前体细胞
Keywords:
oxaliplatin; depression; medial prefrontal cortex; oligodendrocyte precursor cells
分类号:
R979.1
DOI:
10.16571/j.cnki.2097-2768.2025.01.001
文献标志码:
A
摘要:
目的 探究奥沙利铂化疗对小鼠行为的影响，并进一步分析这种影响与小鼠内侧前额叶皮层（mPFC）中的少突胶质细胞前体细胞（OPCs）之间的潜在联系。方法构建奥沙利铂诱导的小鼠抑郁模型，采用随机数字表法将26只小鼠随机分为对照组和奥沙利铂组，每组13只小鼠。在每组中随机选取10只小鼠进行行为学实验，以评估其抑郁样行为，具体通过强迫游泳实验、糖水偏好实验和悬尾实验来完成，另外3只小鼠进行5-溴脱氧尿嘧啶核苷（Brdu）标记实验。在行为学试验结束后，每组随机取4只小鼠，应用免疫荧光技术检测小鼠mPFC中OPCs的密度和增殖情况。将来自SD大鼠的体外培养OPCs用随机数字表法分为对照和不同浓度奥沙利铂处理组（0.25、0.5、1、2 μmol/L），每组4孔，应用免疫荧光技术检测体外大鼠OPCs的增殖情况。结果奥沙利铂组小鼠的强迫游泳实验中不动时间较对照组延长，蔗糖偏好指数较对照组降低，悬尾实验中不动时间较对照组延长，差异均有统计学意义（P<0.05）。第22天时，奥沙利铂组小鼠mPFC区内每平方毫米的OPCs数量及OPCs占总细胞数的比例较对照组明显减少（P<0.05）。第9天时，奥沙利铂组小鼠mPFC区OPCs每平方毫米的数量相较于对照组明显减少（P<0.05），奥沙利铂组小鼠mPFC区域中Brdu+ OPCs占OPCs的比例相较于对照组显著减少（P<0.05）。体外实验显示，各浓度奥沙利铂Brdu+ OPCs占OPCs的比例及Ki67+ OPCs占OPCs的比例较对照明显减少，差异有统计学意义（P<0.01）。结论奥沙利铂化疗可诱导小鼠出现抑郁样行为，降低了小鼠mPFC中OPCs的密度，并抑制了其增殖，OPCs增殖受损与奥沙利铂化疗导致的抑郁样行为之间存在潜在的联系。
Abstract:
Objective To investigate the effect of oxaliplatin chemotherapy on the behavior of mice，and to further analyze thepotential relationship between this effect and oligodendrocyte precursor cells（OPCs）in the medial prefrontal cortex（mPFC）of mice.Methods A depression model was established in mice by the induction of oxaliplatin. Through random number table method，26 micewere randomly divided into control group and oxaliplatin group with13 mice in each group. Ten mice in each group were randomly select?ed for behavioral experiments to assess depression-like behavior，which were completed through forced swimming test，sucrose prefer?ence test and tail suspension test. The remaining 3 mice in each groupwere used for 5-bromo-2?- deoxyuridine（Brdu）labeling experiments.After the behavioral experiment，4 mice were randomly selected fromeach group to detect the density and proliferation of OPCs in mPFC ofmice by immunofluorescence technique. OPCs cultured in vitro from SD rats were divided into control groups and oxaliplatin treatment groups（0.25，0.5，1，2 μmol/L）with different concentrations by ran?dom number table method，with 4 wells in each. The proliferation of OPCs in vitro rats was detected by immunofluorescence tech?nique. Results The immovable time in oxaliplatin group was longer than that in control group in forced swimming test，the sucrosepreference index was lower than that in control group，and the immovable time in tail suspension test was longer than that in controlgroup，the differences were statistically significant（P<0.05）. On day 22，the number of OPCs per square millimeter and the proportionof OPCs to total cell number in mPFC area of oxaliplatin group were significantly decreased compared with control group（P<0.05）. Onday 9，the number of OPCs per square millimeter in mPFC region of mice in oxaliplatin group was significantly reduced compared withcontrol group（P<0.05），and the proportion of Brdu+ OPCs in mPFC region of mice in oxaliplatin group was significantly reduced com?pared with control group（P<0.05）. In vitro experiments showed that the proportion of oxaliplatin Brdu+ OPCs in OPCs and the propor?tion of Ki67+ OPCs in OPCs were significantly decreased compared with the control group，and the difference was statistically signifi?cant（P<0.01）. Conclusion Oxaliplatin chemotherapy can induce depression-like behavior in mice，reduce the density of OPCs inmPFC，and inhibit their proliferation. There is a potential relationship between impaired proliferation of OPCs and depression-like be?havior induced by oxaliplatin chemotherapy.

参考文献/References:

［1］ Vardy J，Wefel JS，Ahles T，et al. Cancer and cancer-therapy re?lated cognitive dysfunction: an international perspective fromthe Venice cognitive workshop［J］. Ann Oncol，2008，19（4）:623-629.［2］ Nordlinger B，Sorbye H，Glimelius B，et al. Perioperative FOLF?OX4 chemotherapy and surgery versus surgery alone for resect?able liver metastases from colorectal cancer（EORTC 40983）:long-term results of a randomised，controlled，phase 3 trial［J］.Lancet Oncol，2013，14（12）: 1208-1215.［3］ Hershman DL，Lacchetti C，Dworkin RH，et al. Prevention andmanagement of chemotherapy-induced peripheral neuropathy insurvivors of adult cancers: American Society of Clinical Oncolo?gy clinical practice guideline［J］. J Clin Oncol，2014，32（18）:1941-1967.［4］ Branca J，Maresca M，Morucci G，et al. Oxaliplatin-induced bloodbrain barrier loosening: a new point of view on chemotherapy-in?duced neurotoxicity［J］.Oncotarget，2018，9（34）: 23426-23438.［5］ Jacobs S，Mccully CL，Murphy RF，et al. Extracellular fluid con?centrations of cisplatin，carboplatin，and oxaliplatin in brain，muscle，and blood measured using microdialysis in nonhumanprimates［J］. Cancer Chemother Pharmacol，2010，65（5）: 817-824.［6］ Rahman AA，Stojanovska V，Pilowsky P，et al. Platinum accumu?lation in the brain and alteration in the central regulation of car?diovascular and respiratory functions in oxaliplatin-treated rats［J］. Pflugers Arch，2021，473（1）: 107-120.［7］ Dietrich J，Han R，Yang Y，et al. CNS progenitor cells and oligo?dendrocytes are targets of chemotherapeutic agents in vitro andin vivo［J］. J Biol，2006，5（7）: 22.［8］ Shabani M，Nazeri M，Parsania S，et al. Walnut consumption pro?tects rats against cisplatin-induced neurotoxicity［J］. Neurotoxi?cology，2012，33（5）: 1314-1321.［9］ Husain K，Whitworth C，Hazelrigg S，et al. Carboplatin-inducedoxidative injury in rat inferior colliculus［J］. Int J Toxicol，2003，22（5）: 335-342.［10］ 徐方宁，刘清珍，张利东. 脑源性神经营养因子与抑郁治疗相关性的研究进展［J］. 医学研究与战创伤救治，2024，37（2）:219-224.［11］ Iarkov A，Appunn D，Echeverria V. Post-treatment with cotinineimproved memory and decreased depressive-like behavior afterchemotherapy in rats［J］. Cancer Chemother Pharmacol，2016，78（5）: 1033-1039.［12］ Rzeski W，Pruskil S，Macke A，et al. Anticancer agents are po?tent neurotoxins in vitro and in vivo［J］. Ann Neurol，2004，56（3）: 351-360.［13］ Bittar TP，Labonté B. Functional Contribution of the Medial Pre?frontal Circuitry in Major Depressive Disorder and Stress-In?duced Depressive-Like Behaviors［J］. Front Behav Neurosci，2021，15: 699592.［14］ 陈佳伟，贾敏，杨建军，等. 抑郁症在不同脑区发生机制的研究进展［J］. 医学研究与战创伤救治，2023，36（6）: 655-660.［15］ Poupon L，Lamoine S，Pereira V，et al. Targeting the TREK-1 po?tassium channel via riluzole to eliminate the neuropathic and de?pressive-like effects of oxaliplatin［J］. Neuropharmacology，2018，140: 43-61.［16］ Micov AM，Tomi? MA，Todorovi? MB，et al. Vortioxetine reducespain hypersensitivity and associated depression-like behavior inmice with oxaliplatin-induced neuropathy［J］. Prog Neuropsycho?pharmacol Biol Psychiatry，2020，103: 109975.［17］ Pachman DR，Qin R，Seisler DK，et al. Clinical Course of Oxali?platin-Induced Neuropathy: Results From the RandomizedPhase III Trial N08CB（Alliance）［J］. J Clin Oncol，2015，33（30）: 3416-3422.［18］ Oh PJ，Lee JR，Kim SK，et al. Changes in chemotherapy-in?duced peripheral neuropathy，disturbance in activities of dailyliving，and depression following chemotherapy in patients withcolorectal cancer: A prospective study［J］. Eur J Oncol Nurs，2020，44: 101676.［19］ Micov AM，Tomi? MA，Todorovi? MB，et al. Vortioxetine reducespain hypersensitivity and associated depression-like behavior inmice with oxaliplatin-induced neuropathy［J］. Prog Neuropsycho?pharmacol Biol Psychiatry，2020，103: 109975.［20］ Poupon L，Lamoine S，Pereira V，et al. Targeting the TREK-1 po?tassium channel via riluzole to eliminate the neuropathic and de?pressive-like effects of oxaliplatin［J］. Neuropharmacology，2018，140: 43-61.［21］ Illias AM，Yu KJ，Hwang SH，et al. Dorsal root ganglion toll-likereceptor 4 signaling contributes to oxaliplatin-induced peripher?al neuropathy［J］. Pain，2022，163（5）: 923-935.［22］ Lorenz J，Minoshima S，Casey KL. Keeping pain out of mind: therole of the dorsolateral prefrontal cortex in pain modulation［J］.Brain，2003，126（Pt 5）: 1079-1091.［23］ Apkarian AV，Sosa Y，Sonty S，et al. Chronic back pain is associ?ated with decreased prefrontal and thalamic gray matter density［J］. J Neurosci，2004，24（46）: 10410-10415.［24］ Devoize L，Alvarez P，Monconduit L，et al. Representation of dy?namic mechanical allodynia in the ventral medial prefrontal cor?tex of trigeminal neuropathic rats［J］. Eur J Pain，2011，15（7）:676-682.［25］ Seamans JK，Lapish CC，Durstewitz D. Comparing the prefrontalcortex of rats and primates: insights from electrophysiology［J］.Neurotox Res，2008，14（2-3）: 249-262.［26］ Banasr M，Duman RS. Glial loss in the prefrontal cortex is suffi?cient to induce depressive-like behaviors［J］. Biol Psychiatry，2008，64（10）: 863-870.［27］ Birey F，Kloc M，Chavali M，et al. Genetic and Stress-Induced Loss of NG2 Glia Triggers Emergence of Depressive-like Behav?iors through Reduced Secretion of FGF2［J］. Neuron，2015，88（5）: 941-956.［28］ Makinodan M，Rosen KM，Ito S，et al. A critical period for socialexperience-dependent oligodendrocyte maturation and myelina?tion［J］. Science，2012，337（6100）: 1357-1360.［29］ Liu J，Dietz K，Deloyht JM，et al. Impaired adult myelination inthe prefrontal cortex of socially isolated mice［J］. Nat Neurosci，2012，15（12）: 1621-1623.［30］ Fernandez-Castaneda A，Gaultier A. Adult oligodendrocyte pro?genitor cells-Multifaceted regulators of the CNS in health anddisease［J］. Brain Behav Immun，2016，57: 1-7.［31］ Fang LP，Bai X. Oligodendrocyte precursor cells: the multitask?ers in the brain［J］. Pflugers Arch，2023，475（9）: 1035-1044.［32］ Auguste Y，Ferro A，Kahng JA，et al. Oligodendrocyte precursorcells engulf synapses during circuit remodeling in mice［J］. NatNeurosci，2022，25（10）: 1273-1278.［33］ Birey F，Kloc M，Chavali M，et al. Genetic and Stress-InducedLoss of NG2 Glia Triggers Emergence of Depressive-like Behav?iors through Reduced Secretion of FGF2［J］. Neuron，2015，88（5）: 941-956.［34］ Kokkosis AG，Madeira MM，Mullahy MR，et al. Chronic stressdisrupts the homeostasis and progeny progression of oligoden?droglial lineage cells，associating immune oligodendrocytes withprefrontal cortex hypomyelination［J］. Mol Psychiatry，2022，27（6）: 2833-2848.［35］ Luo Y，Xiao Q，Wang J，et al. Running exercise protects oligo?dendrocytes in the medial prefrontal cortex in chronic unpredict?able stress rat model［J］. Transl Psychiatry，2019，9（1）: 322.［36］ Nagy C，Maitra M，Tanti A，et al. Single-nucleus transcriptomicsof the prefrontal cortex in major depressive disorder implicatesoligodendrocyte precursor cells and excitatory neurons［J］. NatNeurosci，2020，23（6）: 771-781.［37］ Teissier A，Le Magueresse C，Olusakin J，et al. Early-life stressimpairs postnatal oligodendrogenesis and adult emotional behav?iour through activity-dependent mechanisms［J］. Mol Psychia?try，2020，25（6）: 1159-1174.

相似文献/References:

[1]金 梅,王焕林,陈方斌,等.汶川地震救援官兵中PTSD患者负性情绪表达及相关因素分析[J].医学研究与战创伤救治(原医学研究生学报),2012,14(06):500.
　JIN Mei,WNAG Huan-lin,CHEN Fang-bin,et al.Study on the negative emotions and related factors in military rescuers with PTSD after Wen Chuan earthquake[J].JOURNAL OF MEDICALRESEARCH —COMBAT TRAUMA CARE,2012,14(01):500.
[2]王晓玲,翟金盛,赵迎峰,等.中医治疗脑卒中后抑郁的进展[J].医学研究与战创伤救治(原医学研究生学报),2012,14(01):55.
[3]翟金盛,王晓玲,王 颖.前列腺癌患者社会支持和抑郁状况调查及相关性分析[J].医学研究与战创伤救治(原医学研究生学报),2015,17(01):67.[doi:10.3969/j.issn.1672-271X.2015.01.022]
　ZHAI Jin-sheng,WANG Xiao-ling,WANG Ying..Social support， depression and their correlation in the prostate cancer patients[J].JOURNAL OF MEDICALRESEARCH —COMBAT TRAUMA CARE,2015,17(01):67.[doi:10.3969/j.issn.1672-271X.2015.01.022]
[4]汪琼,周虹.正念减压对系统性淀粉样变性患者知觉压力和焦虑抑郁水平的影响[J].医学研究与战创伤救治(原医学研究生学报),2017,19(04):412.[doi:10.3969/j.issn.1672-271X.2017.04.021]
[5]宋莹莹,张岚,梁瑛琳,等.腰椎间盘突出症患者术后恐动症现状及影响因素分析[J].医学研究与战创伤救治(原医学研究生学报),2019,21(02):205.[doi:10.3969/j.issn.1672-271X.2019.02.022]
[6]张蕾,张睿,薛建良,等.正念训练配合早期强化功能锻炼对胫骨平台骨折患者负性情绪和膝关节功能的影响[J].医学研究与战创伤救治(原医学研究生学报),2021,23(04):350.[doi:10.3969/j.issn.1672-271X.2021.04.003]
　ZHANG Lei,ZHANG Rui,XUE Jian-liang,et al.The effect of mindfulness training combined with early strengthening exercise on negative emotion and knee function in patients with tibial plateau fracture[J].JOURNAL OF MEDICALRESEARCH —COMBAT TRAUMA CARE,2021,23(01):350.[doi:10.3969/j.issn.1672-271X.2021.04.003]
[7]戴为正,吴美娜,傅懋林,等.普拉克索联合高频重复经颅磁刺激治疗早期帕金森病合并抑郁患者的临床疗效观察[J].医学研究与战创伤救治(原医学研究生学报),2021,23(6):592.[doi:10.3969/j.issn.1672-271X.2021.06.007]
　DAI Wei-zheng,WU Mei-na,FU Mao-lin,et al.Observation on clinical effects of pramipexole combined with high-frequency repetitive transcranial magnetic stimulation (rTMS) in the treatment of patients suffered from early Parkinson’s disease (PD) and depression[J].JOURNAL OF MEDICALRESEARCH —COMBAT TRAUMA CARE,2021,23(01):592.[doi:10.3969/j.issn.1672-271X.2021.06.007]
[8]卓兴峰,钟勇,宫剑滨,等.不同降压方案对高血压患者心理评分的影响[J].医学研究与战创伤救治(原医学研究生学报),2023,25(1):54.[doi:10.3969/j.issn.1672-271X.2023.01.011]
　ZHUO Xingfeng,ZHONG Yong,GONG Jianbin,et al.Influence of different antihypertensive programs on psychological score of patients with hypertension[J].JOURNAL OF MEDICALRESEARCH —COMBAT TRAUMA CARE,2023,25(01):54.[doi:10.3969/j.issn.1672-271X.2023.01.011]

备注/Memo

备注/Memo:
基金项目：国家自然科学基金（81971048）
更新日期/Last Update: 2025-01-20