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:

Neurocan regulates vulnerability to stress and the anti-depressant effect of ketamine in adolescent rats

Molecular Psychiatry volume 27, pages 2522–2532 (2022)Cite this article

Subjects

Abstract

Depression is more prevalent among adolescents than adults, but the underlying mechanisms remain largely unknown. Using a subthreshold chronic stress model, here we show that developmentally regulated expressions of the perineuronal nets (PNNs), and one of the components, Neurocan in the prelimbic cortex (PrL) are important for the vulnerability to stress and depressive-like behaviors in both adolescent and adult rats. Reduction of PNNs or Neurocan with pharmacological or viral methods to mimic the expression of PNNs in the PrL during adolescence compromised resilience to stress in adult rats, while virally mediated overexpression of Neurocan reversed vulnerability to stress in adolescent rats. Ketamine, a recent-approved drug for treatment-resistant depression rescued impaired function of Parvalbumin-positive neurons function, increased expression of PNNs in the PrL, and reversed depressive-like behaviors in adolescent rats. Furthermore, we show that Neurocan mediates the anti-depressant effect of ketamine, virally mediated reduction of Neurocan in the PrL abolished the anti-depressant effect of ketamine in adolescent rats. Our findings show an important role of Neurocan in depression in adolescence, and suggest a novel mechanism for the anti-depressant effect of ketamine.

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: Adolescent rats expressed less Neurocan in the PrL and were more prone to SCUMS compared with adults.
Fig. 2: Perineuronal nets degradation in the PrL induced depressive- and anxiety-like behaviors in adult rats.
Fig. 3: shRNA-mediated Neurocan reduction in the PrL increased vulnerability to stress in adult rats.
Fig. 4: Ketamine reversed depressive-like behaviors, elevated PNNs levels, and restored fast-spiking neuron function in the PrL of adolescent rats with SCUMS.
Fig. 5: Expression of Neurocan in the PrL is necessary for the anti-depressant-like effect of ketamine and resilience to stress in adolescent rats.

Similar content being viewed by others

References

  1. Merikangas KR, He JP, Burstein M, Swanson SA, Avenevoli S, Cui L, et al. Lifetime prevalence of mental disorders in U.S. adolescents: results from the National Comorbidity Survey Replication-Adolescent Supplement (NCS-A). J Am Acad Child Adolesc Psychiatry. 2010;49:980–9.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Kessler RC, Avenevoli S, Ries Merikangas K. Mood disorders in children and adolescents: an epidemiologic perspective. Biol Psychiatry. 2001;49:1002–14.

    Article  CAS  PubMed  Google Scholar 

  3. SAMHSA. National Survey on Drug Use and Health 2017 (NSDUH-2017-DS0001). 2018.

  4. Mojtabai R, Olfson M, Han B. National trends in the prevalence and treatment of depression in adolescents and young adults. Pediatrics. 2016;138:e20161878.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Duman RS, Aghajanian GK, Sanacora G, Krystal JH. Synaptic plasticity and depression: new insights from stress and rapid-acting antidepressants. Nat Med. 2016;22:238–49.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Paus T, Keshavan M, Giedd JN. Why do many psychiatric disorders emerge during adolescence? Nat Rev Neurosci. 2008;9:947–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Rakic P, Bourgeois JP, Eckenhoff MF, Zecevic N, Goldman-Rakic PS. Concurrent overproduction of synapses in diverse regions of the primate cerebral cortex. Science. 1986;232:232–5.

    Article  CAS  PubMed  Google Scholar 

  8. Hashimoto T, Nguyen QL, Rotaru D, Keenan T, Arion D, Beneyto M, et al. Protracted developmental trajectories of GABAA receptor alpha1 and alpha2 subunit expression in primate prefrontal cortex. Biol Psychiatry. 2009;65:1015–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Otero Losada ME. Changes in central GABAergic function following acute and repeated stress. Br J Pharm. 1988;93:483–90.

    Article  CAS  Google Scholar 

  10. Tripp A, Oh H, Guilloux JP, Martinowich K, Lewis DA, Sibille E. Brain-derived neurotrophic factor signaling and subgenual anterior cingulate cortex dysfunction in major depressive disorder. Am J Psychiatry. 2012;169:1194–202.

    Article  PubMed  PubMed Central  Google Scholar 

  11. DeFelipe J, Lopez-Cruz PL, Benavides-Piccione R, Bielza C, Larranaga P, Anderson S, et al. New insights into the classification and nomenclature of cortical GABAergic interneurons. Nat Rev Neurosci. 2013;14:202–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Wieck A, Andersen SL, Brenhouse HC. Evidence for a neuroinflammatory mechanism in delayed effects of early life adversity in rats: relationship to cortical NMDA receptor expression. Brain Behav Immun. 2013;28:218–26.

    Article  CAS  PubMed  Google Scholar 

  13. Ho TC, Connolly CG, Henje Blom E, LeWinn KZ, Strigo IA, Paulus MP, et al. Emotion-dependent functional connectivity of the default mode network in adolescent depression. Biol Psychiatry. 2015;78:635–46.

    Article  PubMed  Google Scholar 

  14. Hare TA, Tottenham N, Galvan A, Voss HU, Glover GH, Casey BJ. Biological substrates of emotional reactivity and regulation in adolescence during an emotional go-nogo task. Biol Psychiatry. 2008;63:927–34.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Davey CG, Yucel M, Allen NB. The emergence of depression in adolescence: development of the prefrontal cortex and the representation of reward. Neurosci Biobehav Rev. 2008;32:1–19.

    Article  PubMed  Google Scholar 

  16. Selemon LD. A role for synaptic plasticity in the adolescent development of executive function. Transl Psychiatry. 2013;3:e238.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Whittle S, Lichter R, Dennison M, Vijayakumar N, Schwartz O, Byrne ML, et al. Structural brain development and depression onset during adolescence: a prospective longitudinal study. Am J Psychiatry. 2014;171:564–71.

    Article  PubMed  Google Scholar 

  18. Caballero A, Flores-Barrera E, Cass DK, Tseng KY. Differential regulation of parvalbumin and calretinin interneurons in the prefrontal cortex during adolescence. Brain Struct Funct. 2014;219:395–406.

    Article  CAS  PubMed  Google Scholar 

  19. Page CE, Coutellier L. Adolescent stress disrupts the maturation of anxiety-related behaviors and alters the developmental trajectory of the prefrontal cortex in a sex- and age-specific manner. Neuroscience. 2018;390:265–77.

    Article  CAS  PubMed  Google Scholar 

  20. Lukkes JL, Meda S, Thompson BS, Freund N, Andersen SL. Early life stress and later peer distress on depressive behavior in adolescent female rats: effects of a novel intervention on GABA and D2 receptors. Behav Brain Res. 2017;330:37–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Koppe G, Bruckner G, Brauer K, Hartig W, Bigl V. Developmental patterns of proteoglycan-containing extracellular matrix in perineuronal nets and neuropil of the postnatal rat brain. Cell Tissue Res. 1997;288:33–41.

    Article  CAS  PubMed  Google Scholar 

  22. Bukalo O, Schachner M, Dityatev A. Hippocampal metaplasticity induced by deficiency in the extracellular matrix glycoprotein tenascin-R. J Neurosci. 2007;27:6019–28.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Faissner A, Pyka M, Geissler M, Sobik T, Frischknecht R, Gundelfinger ED, et al. Contributions of astrocytes to synapse formation and maturation—Potential functions of the perisynaptic extracellular matrix. Brain Res Rev. 2010;63:26–38.

    Article  CAS  PubMed  Google Scholar 

  24. Miyata S, Komatsu Y, Yoshimura Y, Taya C, Kitagawa H. Persistent cortical plasticity by upregulation of chondroitin 6-sulfation. Nat Neurosci. 2012;15:414–22. s411-412.

    Article  CAS  PubMed  Google Scholar 

  25. Xue YX, Xue LF, Liu JF, He J, Deng JH, Sun SC, et al. Depletion of perineuronal nets in the amygdala to enhance the erasure of drug memories. J Neurosci. 2014;34:6647–58.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Mauney SA, Athanas KM, Pantazopoulos H, Shaskan N, Passeri E, Berretta S, et al. Developmental pattern of perineuronal nets in the human prefrontal cortex and their deficit in schizophrenia. Biol Psychiatry. 2013;74:427–35.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Cichon S, Muhleisen TW, Degenhardt FA, Mattheisen M, Miro X, Strohmaier J, et al. Genome-wide association study identifies genetic variation in Neurocan as a susceptibility factor for bipolar disorder. Am J Hum Genet. 2011;88:372–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Pantazopoulos H, Woo TU, Lim MP, Lange N, Berretta S. Extracellular matrix-glial abnormalities in the amygdala and entorhinal cortex of subjects diagnosed with schizophrenia. Arch Gen Psychiatry. 2010;67:155–66.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Ueno H, Suemitsu S, Murakami S, Kitamura N, Wani K, Okamoto M, et al. Region-specific impairments in parvalbumin interneurons in social isolation-reared mice. Neuroscience. 2017;359:196–208.

    Article  CAS  PubMed  Google Scholar 

  30. Gomes FV, Zhu X, Grace AA. The pathophysiological impact of stress on the dopamine system is dependent on the state of the critical period of vulnerability. Mol Psychiatry. 2020;25:3278–91.

    Article  CAS  PubMed  Google Scholar 

  31. de Araujo Costa Folha OA, Bahia CP, de Aguiar GPS, Herculano AM, Coelho NLG, de Sousa MBC, et al. Effect of chronic stress during adolescence in prefrontal cortex structure and function. Behav Brain Res. 2017;326:44–51.

    Article  PubMed  Google Scholar 

  32. Ueno H, Suemitsu S, Murakami S, Kitamura N, Wani K, Matsumoto Y, et al. Juvenile stress induces behavioral change and affects perineuronal net formation in juvenile mice. BMC Neurosci. 2018;19:41.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  33. Fawcett JW, Oohashi T, Pizzorusso T. The roles of perineuronal nets and the perinodal extracellular matrix in neuronal function. Nat Rev Neurosci. 2019;20:451–65.

    Article  CAS  PubMed  Google Scholar 

  34. Patris M, Bouchard JM, Bougerol T, Charbonnier JF, Chevalier JF, Clerc G, et al. Citalopram versus fluoxetine: a double-blind, controlled, multicentre, phase III trial in patients with unipolar major depression treated in general practice. Int Clin Psychopharmacol. 1996;11:129–36.

    CAS  PubMed  Google Scholar 

  35. Kurian BT, Ray WA, Arbogast PG, Fuchs DC, Dudley JA, Cooper WO. Effect of regulatory warnings on antidepressant prescribing for children and adolescents. Arch Pediatr Adolesc Med. 2007;161:690–6.

    Article  PubMed  Google Scholar 

  36. Berman RM, Cappiello A, Anand A, Oren DA, Heninger GR, Charney DS, et al. Antidepressant effects of ketamine in depressed patients. Biol Psychiatry. 2000;47:351–4.

    Article  CAS  PubMed  Google Scholar 

  37. Li N, Lee B, Liu RJ, Banasr M, Dwyer JM, Iwata M, et al. mTOR-dependent synapse formation underlies the rapid antidepressant effects of NMDA antagonists. Science. 2010;329:959–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Autry AE, Adachi M, Nosyreva E, Na ES, Los MF, Cheng PF, et al. NMDA receptor blockade at rest triggers rapid behavioural antidepressant responses. Nature. 2011;475:91–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Cullen KR, Amatya P, Roback MG, Albott CS, Westlund Schreiner M, Ren Y, et al. Intravenous ketamine for adolescents with treatment-resistant depression: an open-label study. J Child Adolesc Psychopharmacol. 2018;28:437–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. 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 

  41. Ghosal S, Duman CH, Liu RJ, Wu M, Terwilliger R, Girgenti MJ, et al. Ketamine rapidly reverses stress-induced impairments in GABAergic transmission in the prefrontal cortex in male rodents. Neurobiol Dis. 2020;134:104669.

    Article  CAS  PubMed  Google Scholar 

  42. Ng LHL, Huang Y, Han L, Chang RC, Chan YS, Lai CSW. Ketamine and selective activation of parvalbumin interneurons inhibit stress-induced dendritic spine elimination. Transl Psychiatry. 2018;8:272.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Cardis R, Cabungcal JH, Dwir D, Do KQ, Steullet P. A lack of GluN2A-containing NMDA receptors confers a vulnerability to redox dysregulation: consequences on parvalbumin interneurons, and their perineuronal nets. Neurobiol Dis. 2018;109:64–75.

    Article  CAS  PubMed  Google Scholar 

  44. Yamada J, Ohgomori T, Jinno S. Alterations in expression of Cat-315 epitope of perineuronal nets during normal ageing, and its modulation by an open-channel NMDA receptor blocker, memantine. J Comp Neurol. 2017;525:2035–49.

    Article  CAS  PubMed  Google Scholar 

  45. Yu Z, Chen N, Hu D, Chen W, Yuan Y, Meng S, et al. Decreased density of perineuronal net in prelimbic cortex Is linked to depressive-like behavior in young-aged rats. Front Mol Neurosci. 2020;13:4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Zhang W, Zhang L, Liang B, Schroeder D, Zhang ZW, Cox GA, et al. Hyperactive somatostatin interneurons contribute to excitotoxicity in neurodegenerative disorders. Nat Neurosci. 2016;19:557–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Han Y, Sun CY, Meng SQ, Tabarak S, Yuan K, Cao L, et al. Systemic immunization with altered myelin basic protein peptide produces sustained antidepressant-like effects. Mol Psychiatry. 2020;25:1260–74.

    Article  CAS  PubMed  Google Scholar 

  48. Xue YX, Luo YX, Wu P, Shi HS, Xue LF, Chen C, et al. A memory retrieval-extinction procedure to prevent drug craving and relapse. Science. 2012;336:241–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Zhang W, Daly KM, Liang B, Zhang L, Li X, Li Y, et al. BDNF rescues prefrontal dysfunction elicited by pyramidal neuron-specific DTNBP1 deletion in vivo. J Mol Cell Biol. 2017;9:117–31.

    Article  CAS  PubMed  Google Scholar 

  50. Zhang W, Peterson M, Beyer B, Frankel WN, Zhang ZW. Loss of MeCP2 from forebrain excitatory neurons leads to cortical hyperexcitation and seizures. J Neurosci. 2014;34:2754–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Le Magueresse C, Monyer H. GABAergic interneurons shape the functional maturation of the cortex. Neuron. 2013;77:388–405.

    Article  PubMed  CAS  Google Scholar 

  52. Perova Z, Delevich K, Li B. Depression of excitatory synapses onto parvalbumin interneurons in the medial prefrontal cortex in susceptibility to stress. J Neurosci. 2015;35:3201–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Hartig W, Brauer K, Bruckner G. Wisteria floribunda agglutinin-labelled nets surround parvalbumin-containing neurons. Neuroreport. 1992;3:869–72.

    Article  CAS  PubMed  Google Scholar 

  54. 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 

  55. Clements JA, Nimmo WS, Grant IS. Bioavailability, pharmacokinetics, and analgesic activity of ketamine in humans. J Pharm Sci. 1982;71:539–42.

    Article  CAS  PubMed  Google Scholar 

  56. Maeng S, Zarate CA Jr., Du J, Schloesser RJ, McCammon J, Chen G, et al. Cellular mechanisms underlying the antidepressant effects of ketamine: role of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors. Biol Psychiatry. 2008;63:349–52.

    Article  CAS  PubMed  Google Scholar 

  57. Kawaguchi Y, Kubota Y. Correlation of physiological subgroupings of nonpyramidal cells with parvalbumin- and calbindinD28k-immunoreactive neurons in layer V of rat frontal cortex. J Neurophysiol. 1993;70:387–96.

    Article  CAS  PubMed  Google Scholar 

  58. March J, Silva S, Petrycki S, Curry J, Wells K, Fairbank J, et al. Fluoxetine, cognitive-behavioral therapy, and their combination for adolescents with depression: Treatment for Adolescents With Depression Study (TADS) randomized controlled trial. JAMA. 2004;292:807–20.

    Article  CAS  PubMed  Google Scholar 

  59. Treadway MT, Waskom ML, Dillon DG, Holmes AJ, Park MT, 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 

  60. Karolewicz B, Maciag D, O’Dwyer G, Stockmeier CA, Feyissa AM, Rajkowska G. Reduced level of glutamic acid decarboxylase-67 kDa in the prefrontal cortex in major depression. Int J Neuropsychopharmacol. 2010;13:411–20.

    Article  CAS  PubMed  Google Scholar 

  61. Hasler G, Nugent AC, Carlson PJ, Carson RE, Geraci M, Drevets WC. Altered cerebral gamma-aminobutyric acid type A-benzodiazepine receptor binding in panic disorder determined by [11C]flumazenil positron emission tomography. Arch Gen Psychiatry. 2008;65:1166–75.

    Article  PubMed  Google Scholar 

  62. Amat J, Baratta MV, Paul E, Bland ST, Watkins LR, Maier SF. Medial prefrontal cortex determines how stressor controllability affects behavior and dorsal raphe nucleus. Nat Neurosci. 2005;8:365–71.

    Article  CAS  PubMed  Google Scholar 

  63. Fuchikami M, Thomas A, Liu R, Wohleb ES, Land BB, DiLeone RJ, et al. Optogenetic stimulation of infralimbic PFC reproduces ketamine’s rapid and sustained antidepressant actions. Proc Natl Acad Sci USA. 2015;112:8106–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Morawski M, Bruckner MK, Riederer P, Bruckner G, Arendt T. Perineuronal nets potentially protect against oxidative stress. Exp Neurol. 2004;188:309–15.

    Article  CAS  PubMed  Google Scholar 

  65. Cabungcal JH, Steullet P, Morishita H, Kraftsik R, Cuenod M, Hensch TK, et al. Perineuronal nets protect fast-spiking interneurons against oxidative stress. Proc Natl Acad Sci USA. 2013;110:9130–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Banerjee SB, Gutzeit VA, Baman J, Aoued HS, Doshi NK, Liu RC, et al. Perineuronal nets in the adult sensory cortex are necessary for fear learning. Neuron. 2017;95:169–79 e163.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Gogolla N, Caroni P, Luthi A, Herry C. Perineuronal nets protect fear memories from erasure. Science. 2009;325:1258–61.

    Article  CAS  PubMed  Google Scholar 

  68. Shi W, Wei X, Wang X, Du S, Liu W, Song J, et al. Perineuronal nets protect long-term memory by limiting activity-dependent inhibition from parvalbumin interneurons. Proc Natl Acad Sci USA. 2019;116:27063–73.

    Article  CAS  PubMed Central  Google Scholar 

  69. Rybakowski JK, Skibinska M, Leszczynska-Rodziewicz A, Kaczmarek L, Hauser J. Matrix metalloproteinase-9 gene and bipolar mood disorder. Neuromolecular Med. 2009;11:128–32.

    Article  CAS  PubMed  Google Scholar 

  70. Spijker S, Koskinen MK, Riga D. Incubation of depression: ECM assembly and parvalbumin interneurons after stress. Neurosci Biobehav Rev. 2020;118:65–79.

    Article  PubMed  Google Scholar 

  71. Rogers SL, Rankin-Gee E, Risbud RM, Porter BE, Marsh ED. Normal development of the perineuronal net in humans; in patients with and without epilepsy. Neuroscience. 2018;384:350–60.

    Article  CAS  PubMed  Google Scholar 

  72. Kinney JW, Davis CN, Tabarean I, Conti B, Bartfai T, Behrens MM. A specific role for NR2A-containing NMDA receptors in the maintenance of parvalbumin and GAD67 immunoreactivity in cultured interneurons. J Neurosci. 2006;26:1604–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Donegan JJ, Lodge DJ. Hippocampal perineuronal nets are required for the sustained antidepressant effect of ketamine. Int J Neuropsychopharmacol. 2017;20:354–8.

    CAS  PubMed  Google Scholar 

  74. Xu H, Liu L, Tian Y, Wang J, Li J, Zheng J, et al. A disinhibitory microcircuit mediates conditioned social fear in the prefrontal cortex. Neuron. 2019;102:668–82.e5.

    Article  CAS  PubMed  Google Scholar 

  75. Soiza-Reilly M, Meye FJ, Olusakin J, Telley L, Petit E, Chen X, et al. SSRIs target prefrontal to raphe circuits during development modulating synaptic connectivity and emotional behavior. Mol Psychiatry. 2019;24:726–45.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported in part by National Key Research and Development Program of China (2019YFA0706201, 2019YFC0118604, 2021ZD0202900, and 2017YFC0803608), National Basic Research Program of China (2015CB553503), National Natural Science Foundation of China (32170960, U180220091, 31571099, 81821092, 31741060, and 91732109), and Beijing Municipal Science and Technology Commission (Z181100001518005 and Z161100002616006).

Author information

Author notes

  1. These authors contributed equally: Zhoulong Yu, Ying Han, Die Hu.

Authors and Affiliations

  1. National Institute on Drug Dependence and Beijing Key Laboratory of Drug Dependence, Peking University, Beijing, 100191, China

    Zhoulong Yu, Ying Han, Die Hu, Na Chen, Zhongyu Zhang, Wenxi Chen, Yanxue Xue, Shiqiu Meng, Lin Lu, Wen Zhang & Jie Shi

  2. Peking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), and National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Peking University, Beijing, 100191, China

    Lin Lu

  3. Peking-Tsinghua Center for Life Sciences and PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, 100871, China

    Lin Lu

Authors
  1. Zhoulong Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ying Han
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Die Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Na Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Zhongyu Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Wenxi Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yanxue Xue
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Shiqiu Meng
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Lin Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Wen Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Jie Shi
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

WZ, LL, and JS conceived and designed the experiments. ZY, DH, NC, ZZ, YH, WC, and WZ performed the experiments. ZY, DH, ZZ, and WZ analyzed and interpreted the data. WZ, LL, JS, YH, XY, SM, and ZY wrote the manuscript.

Corresponding authors

Correspondence to Wen Zhang or Jie Shi.

Ethics declarations

Competing interests

The authors declare no competing interests.

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

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yu, Z., Han, Y., Hu, D. et al. Neurocan regulates vulnerability to stress and the anti-depressant effect of ketamine in adolescent rats. Mol Psychiatry 27, 2522–2532 (2022). https://doi.org/10.1038/s41380-022-01495-w

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41380-022-01495-w

This article is cited by

Search

Advanced search

Quick links