Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Myelin-associated oligodendrocytic basic protein-dependent myelin repair confers the long-lasting antidepressant effect of ketamine

Molecular Psychiatry (2023)Cite this article

Subjects

Abstract

Ketamine exhibits rapid and sustained antidepressant effects. As decreased myelination has been linked to depression pathology, changes in myelination may be a pivotal mechanism underlying ketamine’s long-lasting antidepressant effects. Although ketamine has a long-lasting facilitating effect on myelination, the precise roles of myelination in ketamine’s sustained antidepressant effects remain unknown. In this study, we employed spatial transcriptomics (ST) to examine ketamine’s lasting effects in the medial prefrontal cortex (mPFC) and hippocampus of mice subjected to chronic social defeat stress and identified several differentially expressed myelin-related genes. Ketamine’s ability to restore impaired myelination in the brain by promoting the differentiation of oligodendrocyte precursor cells (OPCs) into mature oligodendrocytes was demonstrated. Moreover, we showed that inhibiting the expression of myelin-associated oligodendrocytic basic protein (Mobp) blocked ketamine’s long-lasting antidepressant effects. We also illustrated that α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) signaling mediated ketamine’s facilitation on myelination. In addition, we found that the (R)-stereoisomer of ketamine showed stronger effects on myelination than (S)-ketamine, which may explain its longer-lasting antidepressant effects. These findings reveal novel mechanisms underlying the sustained antidepressant effects of ketamine and the differences in antidepressant effects between (R)-ketamine and (S)-ketamine, providing new insights into the role of myelination in antidepressant mechanisms.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Global spatiotemporal analysis of brains of chronic social defeat stress (CSDS) and ketamine-administered mice.
Fig. 2: Changes in myelination after chronic social defeat stress (CSDS) and ketamine administration.
Fig. 3: Changes in oligodendrocyte precursor cells (OPCs) differentiation and oligodendrocytes generation after chronic social defeat stress (CSDS) and ketamine administration.
Fig. 4: Effects of Mobp inhibition on neurotransmission.
Fig. 5: Effects of increased and decreased myelination on depression and antidepressant effects of ketamine.
Fig. 6: Effects of (R)- and (S)-ketamine on myelination and oligodendrocyte precursor cells differentiation.

Similar content being viewed by others

Data availability

The raw data of RNA sequencing were uploaded to NCBI GEO database.  The address is "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE214861". The access code is "gtaxuwuwbnglhsj". All other data are available in the main text or the Supplementary Material.

References

  1. Zarate CA Jr., Singh JB, Carlson PJ, Brutsche NE, Ameli R, Luckenbaugh DA, et al. A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Arch Gen Psychiatry. 2006;63:856–64.

    Article  CAS  PubMed  Google Scholar 

  2. Kishimoto T, Chawla JM, Hagi K, Zarate CA, Kane JM, Bauer M, et al. Single-dose infusion ketamine and non-ketamine N-methyl-d-aspartate receptor antagonists for unipolar and bipolar depression: a meta-analysis of efficacy, safety and time trajectories. Psychol Med. 2016;46:1459–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Viana GSB, Vale EMD, Araujo ARA, Coelho NC, Andrade SM, Costa ROD, et al. Rapid and long-lasting antidepressant-like effects of ketamine and their relationship with the expression of brain enzymes, BDNF, and astrocytes. Braz J Med Biol Res. 2020;54:e10107.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Wu C, Wang Y, He Y, Wu S, Xie Z, Zhang J, et al. Sub-anesthetic and anesthetic ketamine produce different long-lasting behavioral phenotypes (24 h post-treatment) via inducing different brain-derived neurotrophic factor (BDNF) expression level in the hippocampus. Neurobiol Learn Mem. 2020;167:107136.

    Article  CAS  PubMed  Google Scholar 

  5. Huang C, Wang Y, Wu Z, Xu J, Zhou L, Wang D, et al. miR-98-5p plays a critical role in depression and antidepressant effect of ketamine. Transl Psychiatry. 2021;11:454.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Zhou B, Zhu Z, Ransom BR, Tong X. Oligodendrocyte lineage cells and depression. Mol Psychiatry. 2021;26:103–17.

    Article  PubMed  Google Scholar 

  7. Nagy C, Maitra M, Tanti A, Suderman M, Theroux JF, Davoli MA, et al. Single-nucleus transcriptomics of the prefrontal cortex in major depressive disorder implicates oligodendrocyte precursor cells and excitatory neurons. Nat Neurosci. 2020;23:771–81.

    Article  CAS  PubMed  Google Scholar 

  8. Lehmann ML, Weigel TK, Elkahloun AG, Herkenham M. Chronic social defeat reduces myelination in the mouse medial prefrontal cortex. Sci Rep. 2017;7:46548.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Pascual-Anton R, Blasco-Serra A, Munoz-Moreno E, Pilar-Cuellar F, Garro-Martinez E, Florensa-Zanuy E, et al. Structural connectivity and subcellular changes after antidepressant doses of ketamine and Ro 25-6981 in the rat: an MRI and immuno-labeling study. Brain Struct Funct. 2021;226:2603–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Wang X, Chang L, Wan X, Tan Y, Qu Y, Shan J, et al. (R)-ketamine ameliorates demyelination and facilitates remyelination in cuprizone-treated mice: a role of gut-microbiota-brain axis. Neurobiol Dis. 2022;165:105635.

  11. Weckmann K, Deery MJ, Howard JA, Feret R, Asara JM, Dethloff F, et al. Ketamine’s effects on the glutamatergic and GABAergic systems: a proteomics and metabolomics study in mice. Mol Neuropsychiatry. 2019;5:42–51.

    CAS  PubMed  Google Scholar 

  12. Iram T, Kern F, Kaur A, Myneni S, Morningstar AR, Shin H, et al. Young CSF restores oligodendrogenesis and memory in aged mice via Fgf17. Nature. 2022;605:509–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Yang C, Yang J, Luo A, Hashimoto K. Molecular and cellular mechanisms underlying the antidepressant effects of ketamine enantiomers and its metabolites. Transl Psychiatry. 2019;9:280.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Kougioumtzidou E, Shimizu T, Hamilton NB, Tohyama K, Sprengel R, Monyer H, et al. Signalling through AMPA receptors on oligodendrocyte precursors promotes myelination by enhancing oligodendrocyte survival. Elife. 2017;6:e28080.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Li C, Xiao L, Liu X, Yang W, Shen W, Hu C, et al. A functional role of NMDA receptor in regulating the differentiation of oligodendrocyte precursor cells and remyelination. Glia. 2013;61:732–49.

    Article  PubMed  Google Scholar 

  16. Yao W, Cao Q, Luo S, He L, Yang C, Chen J, et al. Microglial ERK-NRBP1-CREB-BDNF signaling in sustained antidepressant actions of (R)-ketamine. Mol Psychiatry. 2022;27:1618–29.

    Article  CAS  PubMed  Google Scholar 

  17. Yang C, Ren Q, Qu Y, Zhang JC, Ma M, Dong C, et al. Mechanistic target of rapamycin-independent antidepressant effects of (R)-ketamine in a social defeat stress model. Biol Psychiatry. 2018;83:18–28.

    Article  CAS  PubMed  Google Scholar 

  18. Yang C, Qu Y, Fujita Y, Ren Q, Ma M, Dong C, et al. Possible role of the gut microbiota-brain axis in the antidepressant effects of (R)-ketamine in a social defeat stress model. Transl Psychiatry. 2017;7:1294.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Yang C, Kobayashi S, Nakao K, Dong C, Han M, Qu Y, et al. AMPA receptor activation-independent antidepressant actions of ketamine metabolite (S)-norketamine. Biol Psychiatry. 2018;84:591–600.

    Article  CAS  PubMed  Google Scholar 

  20. Yang C, Shirayama Y, Zhang JC, Ren Q, Yao W, Ma M, et al. R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects. Transl Psychiatry. 2015;5:e632.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Zhang JC, Yao W, Dong C, Yang C, Ren Q, Ma M, et al. Comparison of ketamine, 7,8-dihydroxyflavone, and ANA-12 antidepressant effects in the social defeat stress model of depression. Psychopharmacology. 2015;232:4325–35.

    Article  CAS  PubMed  Google Scholar 

  22. Zhang K, Yang C, Chang L, Sakamoto A, Suzuki T, Fujita Y, et al. Essential role of microglial transforming growth factor-beta1 in antidepressant actions of (R)-ketamine and the novel antidepressant TGF-beta1. Transl Psychiatry. 2020;10:32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Wang H, Liu M, Ye Z, Zhou C, Bi H, Wang L, et al. Akt regulates Sox10 expression to control oligodendrocyte differentiation via phosphorylating FoxO1. J Neurosci. 2021;41:8163–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Huang C, Liu T, Wang Q, Hou W, Zhou C, Song Z, et al. Loss of PP2A disrupts the retention of radial glial progenitors in the telencephalic niche to impair the generation for late-born neurons during cortical developmentdagger. Cereb Cortex. 2020;30:4183–96.

    Article  PubMed  Google Scholar 

  25. Wang H, Dong P, He C, Feng XY, Huang Y, Yang WW, et al. Incerta-thalamic circuit controls nocifensive behavior via cannabinoid type 1 receptors. Neuron. 2020;107:538–51.e7.

    Article  CAS  PubMed  Google Scholar 

  26. Liu D, Tang QQ, Wang D, Song SP, Yang XN, Hu SW, et al. Mesocortical BDNF signaling mediates antidepressive-like effects of lithium. Neuropsychopharmacology. 2020;45:1557–66.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Golden SA, Covington HE 3rd, Berton O, Russo SJ. A standardized protocol for repeated social defeat stress in mice. Nat Protoc. 2011;6:1183–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Corriger A, Pickering G. Ketamine and depression: a narrative review. Drug Des Devel Ther. 2019;13:3051–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Belleau EL, Treadway MT, Pizzagalli DA. The impact of stress and major depressive disorder on hippocampal and medial prefrontal cortex morphology. Biol Psychiatry. 2019;85:443–53.

    Article  PubMed  Google Scholar 

  30. Treadway MT, Waskom ML, Dillon DG, Holmes AJ, Park MTM, Chakravarty MM, et al. Illness progression, recent stress, and morphometry of hippocampal subfields and medial prefrontal cortex in major depression. Biol Psychiatry. 2015;77:285–94.

    Article  PubMed  Google Scholar 

  31. Laine MA, Trontti K, Misiewicz Z, Sokolowska E, Kulesskaya N, Heikkinen A, et al. Genetic control of myelin plasticity after chronic psychosocial stress. eNeuro. 2018;5:0166–18.

    Google Scholar 

  32. Carriel V, Campos A, Alaminos M, Raimondo S, Geuna S. Staining methods for normal and regenerative myelin in the nervous system. Methods Mol Biol. 2017;1560:207–18.

    Article  CAS  PubMed  Google Scholar 

  33. Castren E, Monteggia LM. Brain-derived neurotrophic factor signaling in depression and antidepressant action. Biol Psychiatry. 2021;90:128–36.

    Article  CAS  PubMed  Google Scholar 

  34. Lin PY, Ma ZZ, Mahgoub M, Kavalali ET, Monteggia LM. A synaptic locus for TrkB signaling underlying ketamine rapid antidepressant action. Cell Rep. 2021;36:109513.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Casarotto PC, Girych M, Fred SM, Kovaleva V, Moliner R, Enkavi G, et al. Antidepressant drugs act by directly binding to TRKB neurotrophin receptors. Cell. 2021;184:1299–313.e19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Geraghty AC, Gibson EM, Ghanem RA, Greene JJ, Ocampo A, Goldstein AK, et al. Loss of adaptive myelination contributes to methotrexate chemotherapy-related cognitive impairment. Neuron. 2019;103:250–65.e8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Peckham H, Giuffrida L, Wood R, Gonsalvez D, Ferner A, Kilpatrick TJ, et al. Fyn is an intermediate kinase that BDNF utilizes to promote oligodendrocyte myelination. Glia. 2016;64:255–69.

    Article  PubMed  Google Scholar 

  38. Fletcher JL, Wood RJ, Nguyen J, Norman EML, Jun CMK, Prawdiuk AR, et al. Targeting TrkB with a brain-derived neurotrophic factor mimetic promotes myelin repair in the brain. J Neurosci. 2018;38:7088–99.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Li S, Luo X, Hua D, Wang Y, Zhan G, Huang N, et al. Ketamine alleviates postoperative depression-like symptoms in susceptible mice: the role of BDNF-TrkB signaling. Front Pharmacol. 2019;10:1702.

    Article  CAS  PubMed  Google Scholar 

  40. Redman KL, Rechsteiner M. Identification of the long ubiquitin extension as ribosomal protein S27a. Nature. 1989;338:438–40.

    Article  CAS  PubMed  Google Scholar 

  41. Choi I, Zhang Y, Seegobin SP, Pruvost M, Wang Q, Purtell K, et al. Microglia clear neuron-released alpha-synuclein via selective autophagy and prevent neurodegeneration. Nat Commun. 2020;11:1386.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Gong B, Radulovic M, Figueiredo-Pereira ME, Cardozo C. The ubiquitin-proteasome system: potential therapeutic targets for Alzheimer’s disease and spinal cord injury. Front Mol Neurosci. 2016;9:4.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Kam TI, Hinkle JT, Dawson TM, Dawson VL. Microglia and astrocyte dysfunction in Parkinson’s disease. Neurobiol Dis. 2020;144:105028.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Cui Y, Yang Y, Ni Z, Dong Y, Cai G, Foncelle A, et al. Astroglial Kir4.1 in the lateral habenula drives neuronal bursts in depression. Nature. 2018;554:323–7.

    Article  CAS  PubMed  Google Scholar 

  45. Cao P, Chen C, Liu A, Shan Q, Zhu X, Jia C, et al. Early-life inflammation promotes depressive symptoms in adolescence via microglial engulfment of dendritic spines. Neuron. 2021;109:2573–89.e9.

    Article  CAS  PubMed  Google Scholar 

  46. Hu X, Li P, Guo Y, Wang H, Leak RK, Chen S, et al. Microglia/macrophage polarization dynamics reveal novel mechanism of injury expansion after focal cerebral ischemia. Stroke. 2012;43:3063–70.

    Article  CAS  PubMed  Google Scholar 

  47. Zhang M, Wu X, Xu Y, He M, Yang J, Li J, et al. The cystathionine beta-synthase/hydrogen sulfide pathway contributes to microglia-mediated neuroinflammation following cerebral ischemia. Brain Behav Immun. 2017;66:332–46.

    Article  CAS  PubMed  Google Scholar 

  48. Qin C, Fan WH, Liu Q, Shang K, Murugan M, Wu LJ, et al. Fingolimod protects against ischemic white matter damage by modulating microglia toward M2 polarization via STAT3 pathway. Stroke. 2017;48:3336–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Miron VE, Boyd A, Zhao JW, Yuen TJ, Ruckh JM, Shadrach JL, et al. M2 microglia and macrophages drive oligodendrocyte differentiation during CNS remyelination. Nat Neurosci. 2013;16:1211–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Lei Y, Wang J, Wang D, Li C, Liu B, Fang X, et al. SIRT1 in forebrain excitatory neurons produces sexually dimorphic effects on depression-related behaviors and modulates neuronal excitability and synaptic transmission in the medial prefrontal cortex. Mol Psychiatry. 2020;25:1094–111.

    Article  CAS  PubMed  Google Scholar 

  51. Duman RS, Sanacora G, Krystal JH. Altered connectivity in depression: GABA and glutamate neurotransmitter deficits and reversal by novel treatments. Neuron. 2019;102:75–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Zhang JC, Li SX, Hashimoto KR. (-)-ketamine shows greater potency and longer lasting antidepressant effects than S (+)-ketamine. Pharmacol Biochem Behav. 2014;116:137–41.

    Article  CAS  PubMed  Google Scholar 

  53. Zanos P, Moaddel R, Morris PJ, Georgiou P, Fischell J, Elmer GI, et al. NMDAR inhibition-independent antidepressant actions of ketamine metabolites. Nature. 2016;533:481–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Suzuki A, Hara H, Kimura H. Role of the AMPA receptor in antidepressant effects of ketamine and potential of AMPA receptor potentiators as a novel antidepressant. Neuropharmacology. 2023;222:109308.

    Article  CAS  PubMed  Google Scholar 

  55. Gerhard DM, Pothula S, Liu RJ, Wu M, Li XY, Girgenti MJ, et al. GABA interneurons are the cellular trigger for ketamine’s rapid antidepressant actions. J Clin Invest. 2020;130:1336–49.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Wang DS, Penna A, Orser BA. Ketamine increases the function of gamma-aminobutyric acid type A receptors in hippocampal and cortical neurons. Anesthesiology. 2017;126:666–77.

    Article  CAS  PubMed  Google Scholar 

  57. Kato T. Role of mTOR1 signaling in the antidepressant effects of ketamine and the potential of mTORC1 activators as novel antidepressants. Neuropharmacology. 2023;223:109325.

    Article  CAS  PubMed  Google Scholar 

  58. Aguilar-Valles A, De Gregorio D, Matta-Camacho E, Eslamizade MJ, Khlaifia A, Skaleka A, et al. Antidepressant actions of ketamine engage cell-specific translation via eIF4E. Nature. 2021;590:315–9.

    Article  CAS  PubMed  Google Scholar 

  59. Hess EM, Riggs LM, Michaelides M, Gould TD. Mechanisms of ketamine and its metabolites as antidepressants. Biochem Pharmacol. 2022;197:114892.

    Article  CAS  PubMed  Google Scholar 

  60. Robson MJ, Elliott M, Seminerio MJ, Matsumoto RR. Evaluation of sigma (sigma) receptors in the antidepressant-like effects of ketamine in vitro and in vivo. Eur Neuropsychopharmacol. 2012;22:308–17.

    Article  CAS  PubMed  Google Scholar 

  61. Williams NR, Heifets BD, Blasey C, Sudheimer K, Pannu J, Pankow H, et al. Attenuation of antidepressant effects of ketamine by opioid receptor antagonism. Am J Psychiatry. 2018;175:1205–15.

    Article  PubMed  PubMed Central  Google Scholar 

  62. Chen X, Shu S, Bayliss DA. HCN1 channel subunits are a molecular substrate for hypnotic actions of ketamine. J Neurosci. 2009;29:600–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Ma L, Hashimoto K. The role of hippocampal KCNQ2 channel in antidepressant actions of ketamine. Neuron. 2022;110:2201–3.

    Article  CAS  PubMed  Google Scholar 

  64. Voss LJ, Karalus S, Englund V, Sleigh JW. Ketamine action in the in vitro cortical slice is mitigated by potassium channel blockade. Anesthesiology. 2018;128:1167–74.

    Article  CAS  PubMed  Google Scholar 

  65. Zanos P, Moaddel R, Morris PJ, Riggs LM, Highland JN, Georgiou P, et al. Ketamine and ketamine metabolite pharmacology: insights into therapeutic mechanisms. Pharmacol Rev. 2018;70:621–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Yang Y, Cui Y, Sang K, Dong Y, Ni Z, Ma S, et al. Ketamine blocks bursting in the lateral habenula to rapidly relieve depression. Nature. 2018;554:317–22.

    Article  CAS  PubMed  Google Scholar 

  67. Boda E. Myelin and oligodendrocyte lineage cell dysfunctions: new players in the etiology and treatment of depression and stress-related disorders. Eur J Neurosci. 2021;53:281–97.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We acknowledged Mr. Changyong Qi and Ms. Xiaochuan Zou for animal colony maintenance, OEbiotech Inc. for technical support on spatial transcriptomics, and Raygen Health Molecular Medicine Inc. for technical support on in vivo two-photon imaging.

Funding

Funding

This study was supported by grants from the National Natural Science Foundation of China (82271254, 81974171, 82201420, 82070405, 82101270, and 82171189), Innovative and Entrepreneurial Team of Jiangsu Province (JSSCTD202144), Natural Science Foundation of Jiangsu Province (BK20211382 and BK20210975), China Postdoctoral Science Foundation (2021M701496), and Japan Society for the Promotion of Science (21H02846).

Author information

Author notes

  1. These authors contributed equally: Chaoli Huang, Zifeng Wu, Di Wang

Authors and Affiliations

  1. Department of Anesthesiology and Perioperative Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China

    Chaoli Huang, Zifeng Wu, Di Wang, Yuanyuan Wang, Hanyu Liu, Teng He, Cunming Liu & Chun Yang

  2. State Key Laboratory of Pharmaceutical Biotechnology, Model Animal Research Center, Nanjing University, Nanjing, 210061, China

    Chaoli Huang & Guiquan Chen

  3. Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, 260-8670, Japan

    Youge Qu & Kenji Hashimoto

  4. Department of Physiology, School of Medicine, Jinan University, Guangzhou, 510632, China

    Jichun Zhang

  5. Department of Radiation Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China

    Riyue Jiang

  6. Nhwa Institute of Pharmaceutical Research, Jiangsu Nhwa Pharmaceutical Co., Ltd and Jiangsu Key Laboratory of Central Nervous System Drug Research and Development, Xuzhou, 221116, China

    Xiangqing Xu & Xiangyang Xu

  7. Department of Anesthesiology, Pain and Perioperative Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450000, China

    Jian-jun Yang

Authors
  1. Chaoli Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zifeng Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Di Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Youge Qu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jichun Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Riyue Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Xiangqing Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Xiangyang Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Yuanyuan Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Hanyu Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Teng He
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Cunming Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Guiquan Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Jian-jun Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Kenji Hashimoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Chun Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

CY, KH and J-jY contributed to the conception of the study; CY, KH, J-jY, CL and GC designed experiments. KH, CL and GC provided samples and reagents; CH, DW, ZW, YQ, JZ, RJ, XQX, XX, YW, HL and TH performed the experiments; ZW, DW and CH contributed to data analysis; CY, KH, CH, ZW and DW wrote the manuscript. All the authors approved the submission.

Corresponding authors

Correspondence to Jian-jun Yang, Kenji Hashimoto or Chun Yang.

Ethics declarations

Competing interests

CY has received research support from Nhwa. KH is the inventor of filed patent applications on “The use of R-Ketamine in the treatment of psychiatric diseases”, “(S)-norketamine and salt thereof as pharmaceutical”, “R-Ketamine and derivative thereof as prophylactic or therapeutic agent for neurodegeneration disease or recognition function disorder”, “Preventive or therapeutic agent and pharmaceutical composition for inflammatory diseases or bone diseases”, and “R-Ketamine and its derivatives as a preventive or therapeutic agent for a neurodevelopmental disorder” by the Chiba University. KH has also received speakers’ honoraria, consultant fee, or research support from Abbott, Meiji Seika Pharma, Seikagaku Corporation, Sumitomo Pharma, Taisho, Otsuka, Murakami Farm and Perception Neuroscience. Other authors declare no conflict of interest.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Huang, C., Wu, Z., Wang, D. et al. Myelin-associated oligodendrocytic basic protein-dependent myelin repair confers the long-lasting antidepressant effect of ketamine. Mol Psychiatry (2023). https://doi.org/10.1038/s41380-023-02288-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1038/s41380-023-02288-5

This article is cited by

Search

Advanced search

Quick links