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艾司氯胺酮通过海马BDNF-TrkB通路改善神经病理性疼痛所致小鼠工作记忆障碍

蒋玉斌 王星明 张跃 周志强 杨建军

蒋玉斌, 王星明, 张跃, 周志强, 杨建军. 艾司氯胺酮通过海马BDNF-TrkB通路改善神经病理性疼痛所致小鼠工作记忆障碍[J]. 协和医学杂志. doi: 10.12290/j.issn.1674-9081.2023-0581
引用本文: 蒋玉斌, 王星明, 张跃, 周志强, 杨建军. 艾司氯胺酮通过海马BDNF-TrkB通路改善神经病理性疼痛所致小鼠工作记忆障碍[J]. 协和医学杂志. doi: 10.12290/j.issn.1674-9081.2023-0581
JIANG Yubin, WANG Xingming, ZHANG Yue, ZHOU Zhiqiang, YANG Jianjun. Esketamine Improves Working Memory Impairment in Neuropathic Mice Through Hippocampal BDNF-TrkB Pathway[J]. Medical Journal of Peking Union Medical College Hospital. doi: 10.12290/j.issn.1674-9081.2023-0581
Citation: JIANG Yubin, WANG Xingming, ZHANG Yue, ZHOU Zhiqiang, YANG Jianjun. Esketamine Improves Working Memory Impairment in Neuropathic Mice Through Hippocampal BDNF-TrkB Pathway[J]. Medical Journal of Peking Union Medical College Hospital. doi: 10.12290/j.issn.1674-9081.2023-0581

艾司氯胺酮通过海马BDNF-TrkB通路改善神经病理性疼痛所致小鼠工作记忆障碍

doi: 10.12290/j.issn.1674-9081.2023-0581
基金项目: 

河南省医学科技攻关计划联合共建项目(LHGJ20230212)

详细信息
    通讯作者:

    周志强,E-mail:zq_zhou@sina.com

Esketamine Improves Working Memory Impairment in Neuropathic Mice Through Hippocampal BDNF-TrkB Pathway

Funds: 

Jointly Constructed Project of Henan Province Medical Science and Technology Tackling Key Issues Plan(LHGJ20230212)

  • 摘要: 目的 探究艾司氯胺酮改善神经病理性疼痛所致小鼠工作记忆障碍的作用及可能机制。 方法 将2月龄雄性C57BL/6J小鼠随机均分为5组:假手术+生理盐水组(SN组)、慢性坐骨神经压迫(chronic constriction injury,CCI)+生理盐水组(CN组)、CCI+艾司氯胺酮组(CE组)、CCI+ANA-12组(CA组)、CCI+ANA-12+艾司氯胺酮组(CAE)组,每组10只。采用CCI建立神经病理性疼痛模型,于造模后第16天,CE组、CAE组分别给予艾司氯胺酮(10 mg/kg),其中CAE组于艾司氯胺酮注射前半小时给予ANA-12(0.5 mg/kg); CA组仅给予ANA-12; SN组、CN组仅给予等量生理盐水,连续5 d腹腔注射给药。于造模后第21天开始行旷场实验、Y迷宫实验,检测小鼠机械缩足反应阈值(paw withdrawal threshold,PWT)及热缩足潜伏期(paw withdrawal latency,PWL),并于造模后第21~23天腹腔注射溴脱氧尿嘧啶核苷(Bromo-2-deoxyUridine,BrdU)。通过蛋白质免疫印迹实验检测小鼠海马脑源性神经营养因子(brain-derived neurotrophic factor,BDNF)蛋白表达,采用免疫荧光检测海马齿状回BrdU及双皮质素(doublecortin,DCX)共染阳性(BrdU+/DCX+)细胞数量。 结果 与SN组相比,CN组、CE组、CA组、CAE组PWT明显降低(P均<0.05),PWL明显缩短(P均<0.05);在旷场实验中,5组小鼠的运动总距离无明显差异(P=0.142); Y迷宫实验中,与SN组相比,CN组自发性交替正确率明显降低(P<0.001),与CN组相比,CE组自发性交替正确率明显升高(P<0.001),与CE组相比,CAE组自发性交替正确率明显降低(P=0.004);与SN组相比,CN组BDNF表达下调(P=0.021),与CN组相比,CE组BDNF表达上调(P=0.030),与CE组相比,CAE组表达下调(P=0.043);与SN组相比,CN组BrdU+/DCX+细胞数量明显降低(P=0.025),与CN组相比,CE组BrdU+/DCX+细胞数量明显升高(P=0.003),与CE组相比,CAE组BrdU+/DCX+细胞数量明显降低(P=0.014)。 结论 艾司氯胺酮可能通过海马BDNF-TrkB神经通路促进海马齿状回神经再生进而改善神经病理性疼痛所致的工作记忆障碍。
  • [1] Mazza S, Frot M, Rey AE. A comprehensive literature review of chronic pain and memory [J]. Prog Neuropsychopharmacol Biol Psychiatry, 2018, 87: 183-192.
    [2] Miller EK, Lundqvist M, Bastos AM. Working Memory 2.0[J].Neuron. 2018, 100: 463-475.
    [3] Evidence for working memory deficits in chronic pain: a systematic review and meta-analysis. Pain. 2013;154(8):1181-1196.
    [4] Zhang GF, Zhou ZQ, Guo J, et al. Histone deacetylase 3 in hippocampus contributes to memory impairment after chronic constriction injury of sciatic nerve in mice [J]. Pain. 2021, 162: 382-395.
    [5] Wei Y, Chang L, Hashimoto K. Molecular mechanisms underlying the antidepressant actions of arketamine: beyond the NMDA receptor [J]. Mol Psychiatry. 2022, 27: 559-573.
    [6] Wei Y, Chang L, Hashimoto K. A historical review of antidepressant effects of ketamine and its enantiomers [J]. Pharmacol Biochem Behav. 2020, 190: 172870.
    [7] Zhang C, He J, Shi Q, et al. Subanaesthetic dose of esketamine during induction delays anaesthesia recovery a randomized, double-blind clinical trial [J]. BMC anesthesiology. 2022, 22: 138.
    [8] Hashimoto K. Arketamine for cognitive impairment in psychiatric disorders. Eur Arch Psychiatry Clin Neurosci [J]. 2023, 273: 1513-1525.
    [9] Zhang K, Yao Y, Hashimoto K. Ketamine and its metabolites: Potential as novel treatments for depression. Neuropharmacology [J]. 2023, 222: 109305.
    [10] Xia SH, Hu SW, Ge DG, et al. Chronic Pain Impairs Memory Formation via Disruption of Neurogenesis Mediated by Mesohippocampal Brain-Derived Neurotrophic Factor Signaling [J]. Biological psychiatry. 2020, 88: 597-610.
    [11] Wu A, Zhang J. Neuroinflammation, memory, and depression: new approaches to hippocampal neurogenesis [J]. J Neuroinflammation. 2023, 20: 283.
    [12] Wang XM, Zhang GF, Jia M, et al. Environmental enrichment improves pain sensitivity, depressionlike phenotype, and memory deficit in mice with neuropathic pain: role of NPAS4. Psychopharmacology (Berl) [J]. 2019, 236: 1999-2014.
    [13] Hussain G, Akram R, Anwar H, et al. Adult neurogenesis: a real hope or a delusion? Neural Regen Res [J]. 2024, 19: 6-15.
    [14] Jaberi S, Fahnestock M. Mechanisms of the Beneficial Effects of Exercise on Brain-Derived Neurotrophic Factor Expression in Alzheimer's Disease [J]. Biomolecules. 2023, 13: 1577.
    [15] 李亚南, 张琦, 于家旭, 尹春平, 等. BDNF/TrkB信号通路在预先注射青年大鼠血浆减轻七氟烷诱发老龄大鼠认知功能障碍中的作用[J]. 中华麻醉学杂志, 2022, 42: 546-550.
    [16] Fabrazzo M, Cipolla S, Pisaturo M, et al. Bidirectional Relationship between HIV/HBV Infection and Comorbid Depression and/or Anxiety: A Systematic Review on Shared Biological Mechanisms. J Pers Med. 2023;13(12):1689
    [17] Pettorruso M, Miuli A, Clemente K, et al. Enhanced peripheral levels of BDNF and proBDNF: elucidating neurotrophin dynamics in cocaine use disorder. Mol Psychiatry. Published online January 4, 2024.
    [18] Zhang S, Chen Y, Wang Y, Wang H, Yao D, Chen G. Tau Accumulation in the Spinal Cord Contributes to Chronic Inflammatory Pain by Upregulation of IL-1β and BDNF. Neurosci Bull. Published online December 26, 2023
    [19] Cook AA, Leung TCS, Rice M, Nachman M, Zadigue-Dube É, Watt AJ. Endosomal dysfunction contributes to cerebellar deficits in spinocerebellar ataxia type 6. Elife. 2023;12:RP90510. Published 2023 Dec 12.
    [20] Borsellino P, Krider RI, Chea D, et al. Ketamine and the Disinhibition Hypothesis: Neurotrophic Factor-Mediated Treatment of Depression. Pharmaceuticals (Basel) [J]. 2023, 16: 742.
    [21] Medeiros GC, Gould TD, Prueitt WL, et al. Blood-based biomarkers of antidepressant response to ketamine and esketamine: A systematic review and meta-analysis [J]. Mol Psychiatry. 2022, 27: 3658-3669.
    [22] Zeng J, Xie Z, Chen L, et al. Rosmarinic acid alleviate CORT-induced depressive-like behavior by promoting neurogenesis and regulating BDNF/TrkB/PI3K signaling axis. Biomed Pharmacother. Published online December 8, 2023.
    [23] Huang EJ, Reichardt LF. Trk receptors: roles in neuronal signal transduction. Annu Rev Biochem. 2003;72:609-642.
    [24] Carvalho AL, Caldeira MV, Santos SD, Duarte CB. Role of the brain-derived neurotrophic factor at glutamatergic synapses. Br J Pharmacol. 2008;153 Suppl 1(Suppl 1):S310-S324.
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出版历程
  • 收稿日期:  2023-11-30
  • 录用日期:  2024-01-09
  • 网络出版日期:  2024-03-01

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