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Brain interleukin-1 mediates chronic stress-induced depression in mice via adrenocortical activation and hippocampal neurogenesis suppression

Abstract

Several lines of evidence implicate the pro-inflammatory cytokine interleukin-1 (IL-1) in the etiology and pathophysiology of major depression. To explore the role of IL-1 in chronic stress-induced depression and some of its underlying biological mechanisms, we used the chronic mild stress (CMS) model of depression. Mice subjected to CMS for 5 weeks exhibited depressive-like symptoms, including decreased sucrose preference, reduced social exploration and adrenocortical activation, concomitantly with increased IL-1β levels in the hippocampus. In contrast, mice with deletion of the IL-1 receptor type I (IL-1rKO) or mice with transgenic, brain-restricted overexpression of IL-1 receptor antagonist did not display CMS-induced behavioral or neuroendocrine changes. Similarly, whereas in wild-type (WT) mice CMS significantly reduced hippocampal neurogenesis, measured by incorporation of bromodeoxyuridine (BrdU) and by doublecortin immunohistochemistry, no such decrease was observed IL-1rKO mice. The blunting of the adrenocortical activation in IL-1rKO mice may play a causal role in their resistance to depression, because removal of endogenous glucocorticoids by adrenalectomy also abolished the depressive-like effects of CMS, whereas chronic administration of corticosterone for 4 weeks produced depressive symptoms and reduced neurogenesis in both WT and IL-1rKO mice. The effects of CMS on both behavioral depression and neurogenesis could be mimicked by exogenous subcutaneous administration of IL-1β via osmotic minipumps for 4 weeks. These findings indicate that elevation in brain IL-1 levels, which characterizes many medical conditions, is both necessary and sufficient for producing the high incidence of depression found in these conditions. Thus, procedures aimed at reducing brain IL-1 levels may have potent antidepressive actions.

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References

  1. Yirmiya R . Behavioral and psychological effects of immune activation: implications for ‘depression due to a general medical condition’. Curr Opin Psychiatry 1997; 10: 470–476.

    Article  Google Scholar 

  2. Dantzer R, Wollman E, Vitkovic L, Yirmiya R . Cytokines and depression: fortuitous or causative association? Mol Psychiatry 1999; 4: 328–332.

    Article  CAS  PubMed  Google Scholar 

  3. Schiepers OJ, Wichers MC, Maes M . Cytokines and major depression. Prog Neuropsychopharmacol Biol Psychiatry 2005; 29: 201–217.

    Article  CAS  PubMed  Google Scholar 

  4. Hayley S, Poulter MO, Merali Z, Anisman H . The pathogenesis of clinical depression: stressor- and cytokine-induced alterations of neuroplasticity. Neuroscience 2005; 135: 659–678.

    Article  CAS  PubMed  Google Scholar 

  5. Levine J, Barak Y, Chengappa KN, Rapoport A, Rebey M, Barak V . Cerebrospinal cytokine levels in patients with acute depression. Neuropsychobiology 1999; 40: 171–176.

    Article  CAS  PubMed  Google Scholar 

  6. Owen BM, Eccleston D, Ferrier IN, Young AH . Raised levels of plasma interleukin-1beta in major and postviral depression. Acta Psychiatr Scand 2001; 103: 226–228.

    Article  CAS  PubMed  Google Scholar 

  7. Thomas AJ, Davis S, Morris C, Jackson E, Harrison R, O'Brien JT . Increase in interleukin-1beta in late-life depression. Am J Psychiat 2005; 162: 157–175.

    Google Scholar 

  8. Brambilla F, Monteleone P, Maj M . Interleukin-1beta and tumor necrosis factor-alpha in children with major depressive disorder or dysthymia. J Affect Disord 2004; 78: 273–277.

    Article  CAS  PubMed  Google Scholar 

  9. Anisman H, Ravindran AV, Griffiths J, Merali Z . Endocrine and cytokine correlates of major depression and dysthymia with typical or atypical features. Mol Psychiatry 1999; 4: 182–188.

    Article  CAS  PubMed  Google Scholar 

  10. Musselman DL, Lawson DH, Gumnick JF, Manatunga AK, Penna S, Goodkin RS et al. Paroxetine for the prevention of depression induced by high-dose interferon alfa. N Engl J Med 2001; 344: 961–966.

    Article  CAS  PubMed  Google Scholar 

  11. Capuron L, Miller AH . Cytokines and psychopathology: lessons from interferon-alpha. Biol Psychiatry 2004; 56: 819–824.

    Article  CAS  PubMed  Google Scholar 

  12. Yu YW, Chen TJ, Hong CJ, Chen HM, Tsai SJ . Association study of the interleukin-1 beta (C-511T) genetic polymorphism with major depressive disorder, associated symptomatology, and antidepressant response. Neuropsychopharmacology 2003; 28: 1182–1185.

    Article  CAS  PubMed  Google Scholar 

  13. Morag M, Yirmiya R, Lerer B, Morag A . Influence of socioeconomic status on behavioral, emotional and cognitive effects of rubella vaccination: a prospective, double blind study. Psychoneuroendocrinology 1998; 23: 337–351.

    Article  CAS  PubMed  Google Scholar 

  14. Reichenberg A, Yirmiya R, Schuld A, Kraus T, Haack M, Pollmacher T . Endotoxin-induced emotional and cognitive disturbances in healthy volunteers are associated with increased plasma levels of cytokines and cortisol. Arch Gen Psychiatry 2001; 58: 445–452.

    Article  CAS  PubMed  Google Scholar 

  15. Shapira-Lichter I, Beilin B, Bessler H, Ailon K, Ballas M, Shavit Y et al. Inflammatory cytokines and cholinergic signaling modulate stress-induced alterations in mood and cognition. Neural Plast 2004; 12: 55–56.

    Google Scholar 

  16. Yirmiya R . Endotoxin produces a depressive-like episode in rats. Brain Res 1996; 711: 163–174.

    Article  CAS  PubMed  Google Scholar 

  17. Yirmiya R, Pollak Y, Barak O, Avitsur R, Ovadia H, Bette M et al. Effects of antidepressant drugs on the behavioral and physiological responses to lipopolysaccharide (LPS) in rodents. Neuropsychopharmacology 2001; 24: 531–544.

    Article  CAS  PubMed  Google Scholar 

  18. Castanon N, Bluthe RM, Dantzer R . Chronic treatment with the atypical antidepressant tianeptine attenuates sickness behavior induced by peripheral but not central lipopolysaccharide and interleukin-1beta in the rat. Psychopharmacology (Berl) 2001; 154: 50–60.

    Article  CAS  Google Scholar 

  19. Merali Z, Brennan K, Brau P, Anisman H . Dissociating anorexia and anhedonia elicited by interleukin-1beta: antidepressant and gender effects on responding for ‘free chow’ and ‘earned’ sucrose intake. Psychopharmacology (Berl) 2003; 165: 413–418.

    Article  CAS  Google Scholar 

  20. Yirmiya R, Weidenfeld J, Pollak Y, Morag M, Morag A, Avitsur R et al. Cytokines, ‘depression due to a general medical condition,’ and antidepressant drugs. Adv Exp Med Biol 1999; 461: 283–316.

    Article  CAS  PubMed  Google Scholar 

  21. Dantzer R . Cytokine-induced sickness behavior: where do we stand? Brain Behav Immun 2001; 15: 7–24.

    Article  CAS  PubMed  Google Scholar 

  22. Pollak Y, Yirmiya R . Cytokine-induced changes in mood and behavior: implications for ‘depression due to a general medical condition’, immunotherapy and antidepressive treatment. Int J Neuropsychopharmacol 2002; 5: 389–399.

    Article  CAS  PubMed  Google Scholar 

  23. Heinz A, Hermann D, Smolka MN, Rieks M, Graf KJ, Pohlau D et al. Effects of acute psychological stress on adhesion molecules, interleukins and sex hormones: implications for coronary heart disease. Psychopharmacology (Berl) 2003; 165: 111–117.

    Article  CAS  Google Scholar 

  24. Waschul B, Herforth A, Stiller-Winkler R, Idel H, Granrath N, Deinzer R . Effects of plaque, psychological stress and gender on crevicular IL-1beta and IL-1ra secretion. J Clin Periodontol 2003; 30: 238–248.

    Article  PubMed  Google Scholar 

  25. Deinzer R, Forster P, Fuck L, Herforth A, Stiller-Winkler R, Idel H . Increase of crevicular interleukin 1beta under academic stress at experimental gingivitis sites and at sites of perfect oral hygiene. J Clin Periodontol 1999; 26: 1–8.

    Article  CAS  PubMed  Google Scholar 

  26. Deinzer R, Kottmann W, Forster P, Herforth A, Stiller-Winkler R, Idel H . After-effects of stress on crevicular interleukin-1beta. J Clin Periodontol 2000; 27: 74–77.

    Article  CAS  PubMed  Google Scholar 

  27. Shintani F, Nakaki T, Kanba S, Sato K, Yagi G, Shiozawa M et al. Involvement of interleukin-1 in immobilization stress-induced increase in plasma adrenocorticotropic hormone and in release of hypothalamic monoamines in the rat. J Neurosci 1995; 15: 1961–1970.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Nguyen KT, Deak T, Owens SM, Kohno T, Fleshner M, Watkins LR et al. Exposure to acute stress induces brain interleukin-1b protein in the rat. J Neurosci 1998; 18: 2239–2246.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. O'Connor KA, Johnson JD, Hansen MK, Wieseler Frank JL, Maksimova E, Watkins LR et al. Peripheral and central proinflammatory cytokine response to a severe acute stressor. Brain Res 2003; 991: 123–132.

    Article  CAS  PubMed  Google Scholar 

  30. Maier SF, Watkins LR . Intracerebroventricular interleukin-1 receptor antagonist blocks the enhancement of fear conditioning and interference with escape produced by inescapable shock. Brain Res 1995; 695: 279–282.

    Article  CAS  PubMed  Google Scholar 

  31. Pugh CR, Fleshner M, Watkins LR, Maier SF, Rudy JW . The immune system and memory consolidation: a role for the cytokine IL-1β. Neurosci Biobehav Rev 2001; 25: 29–41.

    Article  Google Scholar 

  32. Goshen I, Yirmiya R, Iverfeldt K, Weidenfeld J . The role of endogenous interleukin-1 in stress-induced adrenal activation and adrenalectomy-induced adrenocorticotropic hormone hypersecretion. Endocrinology 2003; 144: 4453–4458.

    Article  CAS  PubMed  Google Scholar 

  33. Kessler RC . The effects of stressful life events on depression. Annu Rev Psychol 1997; 48: 191–214.

    Article  CAS  PubMed  Google Scholar 

  34. Kendler KS, Karkowski LM, Prescott CA . Causal relationship between stressful life events and the onset of major depression. Am J Psychiatry 1999; 156: 837–841.

    Article  CAS  PubMed  Google Scholar 

  35. Caspi A, Sugden K, Moffitt TE, Taylor A, Craig IW, Harrington H et al. Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene. Science 2003; 301: 386–389.

    Article  CAS  PubMed  Google Scholar 

  36. Duval F, Mokrani MC, Monreal-Ortiz JA, Fattah S, Champeval C, Schulz P et al. Cortisol hypersecretion in unipolar major depression with melancholic and psychotic features: dopaminergic, noradrenergic and thyroid correlates. Psychoneuroendocrinology 2006; 31: 876–888.

    Article  CAS  PubMed  Google Scholar 

  37. Barden N, Reul JM, Holsboer F . Do antidepressants stabilize mood through actions on the hypothalamic–pituitary–adrenocortical system? Trends Neurosci 1995; 18: 6–11.

    Article  CAS  PubMed  Google Scholar 

  38. Carroll BJ . The dexamethasone suppression test for melancholia. Br J Psychiatry 1982; 140: 292–304.

    Article  CAS  PubMed  Google Scholar 

  39. Schmid DA, Wichniak A, Uhr M, Ising M, Brunner H, Held K et al. Changes of sleep architecture, spectral composition of sleep EEG, the nocturnal secretion of cortisol, ACTH, GH, prolactin, melatonin, ghrelin, and leptin, and the DEX-CRH test in depressed patients during treatment with mirtazapine. Neuropsychopharmacology 2006; 31: 832–844.

    Article  CAS  PubMed  Google Scholar 

  40. Young EA, Altemus M, Lopez JF, Kocsis JH, Schatzberg AF, DeBattista C et al. HPA axis activation in major depression and response to fluoxetine: a pilot study. Psychoneuroendocrinology 2004; 29: 1198–1204.

    Article  CAS  PubMed  Google Scholar 

  41. Reul JM, Stec I, Soder M, Holsboer F . Chronic treatment of rats with the antidepressant amitriptyline attenuates the activity of the hypothalamic–pituitary–adrenocortical system. Endocrinology 1993; 133: 312–320.

    Article  CAS  PubMed  Google Scholar 

  42. Holsboer F, Liebl R, Hofschuster E . Repeated dexamethasone suppression test during depressive illness. Normalisation of test result compared with clinical improvement. J Affect Disord 1982; 4: 93–101.

    Article  CAS  PubMed  Google Scholar 

  43. Jacobs BL, Praag H, Gage FH . Adult brain neurogenesis and psychiatry: a novel theory of depression. Mol Psychiatry 2000; 5: 262–269.

    Article  CAS  PubMed  Google Scholar 

  44. Kempermann G, Kronenberg G . Depressed new neurons—adult hippocampal neurogenesis and a cellular plasticity hypothesis of major depression. Biol Psychiatry 2003; 54: 499–503.

    Article  PubMed  Google Scholar 

  45. Monje ML, Toda H, Palmer TD . Inflammatory blockade restores adult hippocampal neurogenesis. Science 2003; 302: 1760–1765.

    Article  CAS  PubMed  Google Scholar 

  46. Ekdahl CT, Claasen JH, Bonde S, Kokaia Z, Lindvall O . Inflammation is detrimental for neurogenesis in adult brain. Proc Natl Acad Sci USA 2003; 100: 13632–13637.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Willner P . Validity, reliability and utility of the chronic mild stress model of depression: a 10-year review and evaluation. Psychopharmacology (Berl) 1997; 134: 319–329.

    Article  CAS  Google Scholar 

  48. Willner P . Chronic mild stress (CMS) revisited: consistency and behavioural-neurobiological concordance in the effects of CMS. Neuropsychobiology 2005; 52: 90–110.

    Article  CAS  PubMed  Google Scholar 

  49. Labow M, Shuster D, Zetterstorm M, Nunes P, Terry R, Cullinan EB et al. Absence of IL-1 signaling and reduced inflammatory response in IL-1 type I receptor-deficient mice. J Immunol 1997; 159: 2452–2461.

    CAS  PubMed  Google Scholar 

  50. Avital A, Goshen I, Kamsler A, Segal M, Iverfeldt K, Richter-Levin G et al. Impaired interleukin-1 signaling is associated with deficits in hippocampal memory processes and neural plasticity. Hippocampus 2003; 13: 826–834.

    Article  CAS  PubMed  Google Scholar 

  51. Lundkvist J, Sundgren-Andersson AK, Tingsborg S, Ostlund P, Engfors C, Alheim K et al. Acute-phase response in transgenic mice with CNS overexpression of IL-1 receptor antagonist. Am J Physiol 1999; 276: R644–R651.

    CAS  PubMed  Google Scholar 

  52. Bajayo A, Goshen I, Feldman S, Csernus V, Iverfeldt K, Shohami E et al. Central IL-1 receptor signaling regulates bone growth and mass. Proc Natl Acad Sci USA 2005; 102: 12956–12961.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Wolf G, Yirmiya R, Goshen I, Iverfeldt K, Holmlund L, Takeda K et al. Impairment of interleukin-1 (IL-1) signaling reduces basal pain sensitivity in mice: genetic, pharmacological and developmental aspects. Pain 2003; 104: 471–480.

    Article  CAS  PubMed  Google Scholar 

  54. Tehranian R, Andell-Jonsson S, Beni SM, Yatsiv I, Shohami E, Bartfai T et al. Improved recovery and delayed cytokine induction after closed head injury in mice with central overexpression of the secreted isoform of the interleukin-1 receptor antagonist. J Neurotrauma 2002; 19: 939–951.

    Article  PubMed  Google Scholar 

  55. Weidenfeld J, Yirmiya R . Effects of bacterial endotoxin on the glucocorticoid feedback regulation of adrenocortical response to stress. Neuroimmunomodulation 1996; 3: 352–357.

    Article  CAS  PubMed  Google Scholar 

  56. Sapolsky RM, Krey LC, McEwen BS . Prolonged glucocorticoid exposure reduces hippocampal neuron number: implications for aging. J Neurosci 1985; 5: 1222–1227.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Lippuner K, del Pozo E, MacKenzie A, Jaeger Ph . Long-term systemic administration of human recombinant interleukin-1B induces a dose-dependent fall in circulating parathyroid hormone in rats. Horm Res 1999; 51: 74–77.

    CAS  PubMed  Google Scholar 

  58. Koide M, Suda S, Saitoh S, Ofuji Y, Suzuki T, Yoshie H et al. In vivo administration of IL-1 beta accelerates silk ligature-induced alveolar bone resorption in rats. J Oral Pathol Med 1995; 24: 420–434.

    Article  CAS  PubMed  Google Scholar 

  59. Gillespie CF, Nemeroff CB . Hypercortisolemia and depression. Psychosom Med 2005; 67: S26–S28.

    Article  PubMed  Google Scholar 

  60. Duman RS . Depression: a case of neuronal life and death? Biol Psychiatry 2004; 56: 140–145.

    Article  PubMed  Google Scholar 

  61. Nestler EJ, Barrot M, DiLeone RJ, Eisch AJ, Gold SJ, Monteggia LM . Neurobiology of depression. Neuron 2002; 34: 13–25.

    Article  CAS  PubMed  Google Scholar 

  62. Tanebe K, Nishijo H, Muraguchi A, Ono T . Effects of chronic stress on hypothalamic lnterleukin-1beta, interleukin-2, and gonadotrophin-releasing hormone gene expression in ovariectomized rats. J Neuroendocrinol 2000; 12: 13–21.

    Article  CAS  PubMed  Google Scholar 

  63. Bartolomucci A, Palanza P, Parmigiani S, Pederzani T, Merlot E, Neveu PJ et al. Chronic psychosocial stress down-regulates central cytokines mRNA. Brain Res Bull 2003; 62: 173–178.

    Article  CAS  PubMed  Google Scholar 

  64. Plata-Salaman CR, Ilyin SE, Turrin NP, Gayle D, Flynn MC, Bedard T et al. Neither acute nor chronic exposure to a naturalistic (predator) stressor influences the interleukin-1beta system, tumor necrosis factor-alpha, transforming growth factor-beta1, and neuropeptide mRNAs in specific brain regions. Brain Res Bull 2000; 51: 187–193.

    Article  CAS  PubMed  Google Scholar 

  65. Mormede C, Castanon N, Medina C, Moze E, Lestage J, Neveu PJ et al. Chronic mild stress in mice decreases peripheral cytokine and increases central cytokine expression independently of IL-10 regulation of the cytokine network. Neuroimmunomodulation 2002-2003; 10: 359–366.

    Article  CAS  PubMed  Google Scholar 

  66. Besedovsky HO, del-Rey A . Immune-neuro-endocrine interactions: facts and hypotheses. Endocr Rev 1996; 17: 64–102.

    Article  CAS  PubMed  Google Scholar 

  67. Wu LM, Han H, Wang QN, Hou HL, Tong H, Yan XB et al. Mifepristone repairs region-dependent alteration of synapsin I in hippocampus in rat model of depression. Neuropsychopharmacology (in press).

  68. Gibbons, McHugh PR . Plasma cortisol in depressive illness. J Psychiatr Res 1962; 1: 162–171.

    Article  CAS  PubMed  Google Scholar 

  69. Sachar EJ, Hellman L, Fukushima DK, Gallagher TF . Cortisol production in depressive illness: a clinical and biochemical clarification. Arch Gen Psychiatry 1970; 23: 289–298.

    Article  CAS  PubMed  Google Scholar 

  70. Berton O, Nestler EJ . New approaches to antidepressant drug discovery: beyond monoamines. Nat Rev Neurosci 2006; 7: 137–151.

    Article  CAS  PubMed  Google Scholar 

  71. Duman RS . Depression: a case of neuronal life and death? Biol Psychiatry 2004; 56: 140–145.

    Article  PubMed  Google Scholar 

  72. Malberg JE, Eisch AJ, Nestler EJ, Duman RS . Chronic antidepressant treatment increases neurogenesis in adult rat hippocampus. J Neurosci 2000; 20: 9104–9110.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Malberg JE . Implications of adult hippocampal neurogenesis in antidepressant action. J Psychiatry Neurosci 2004; 29: 196–205.

    PubMed  PubMed Central  Google Scholar 

  74. Kodama M, Fujioka T, Duman RS . Chronic olanzapine or fluoxetine administration increases cell proliferation in hippocampus and prefrontal cortex of adult rat. Biol Psychiatry 2004; 56: 570–580.

    Article  CAS  PubMed  Google Scholar 

  75. Czeh B, Michaelis T, Watanabe T, Frahm J, de Biurrun G, van Kampen M et al. Stress-induced changes in cerebral metabolites, hippocampal volume, and cell proliferation are prevented by antidepressant treatment with tianeptine. Proc Natl Acad Sci USA 2001; 98: 12796–12801.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Fuchs E, Czeh B, Flugge G . Examining novel concepts of the pathophysiology of depression in the chronic psychosocial stress paradigm in tree shrews. Behav Pharmacol 2004; 15: 315–325.

    Article  CAS  PubMed  Google Scholar 

  77. Alonso R, Griebel G, Pavone G, Stemmelin J, Le Fur G, Soubrie P . Blockade of CRF(1) or V(1b) receptors reverses stress-induced suppression of neurogenesis in a mouse model of depression. Mol Psychiatry 2004; 9: 278–286.

    Article  CAS  PubMed  Google Scholar 

  78. Jayatissa MN, Bisgaard C, Tingstrom A, Papp M, Wiborg O . Hippocampal cytogenesis correlates to escitalopram-mediated recovery in a chronic mild stress rat model of depression. Neuropsychopharmacology 2006; 31: 2395–2404.

    Article  CAS  PubMed  Google Scholar 

  79. Santarelli L, Saxe M, Gross C, Surget A, Battaglia F, Dulawa S et al. Requirement of hippocampal neurogenesis for the behavioral effects of antidepressants. Science 2003; 301: 805–809.

    CAS  PubMed  Google Scholar 

  80. Sheline YI . 3D MRI studies of neuroanatomic changes in unipolar major depression: the role of stress and medical comorbidity. Biol Psychiatry 2000; 48: 791–800.

    Article  CAS  PubMed  Google Scholar 

  81. Campbell S, MacQueen G . The role of the hippocampus in the pathophysiology of major depression. J Psychiatry Neurosci 2004; 29: 417–426.

    PubMed  PubMed Central  Google Scholar 

  82. Vermetten E, Vythilingam M, Southwick SM, Charney DS, Bremner JD . Long-term treatment with paroxetine increases verbal declarative memory and hippocampal volume in posttraumatic stress disorder. Biol Psychiatry 2003; 54: 693–702.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Mirescu C, Gould E . Stress and adult neurogenesis. Hippocampus 2006; 16: 233–238.

    Article  CAS  PubMed  Google Scholar 

  84. Avitsur R, Yirmiya R . The immunobiology of sexual behavior: gender differences in the suppression of sexual activity during illness. Pharmacol Biochem Behav 1999; 64: 787–796.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We thank Professor K Iverfeldt for the IL-1raTG mice. This study was supported by a grant from the Israel Science Foundation (to RY). RY is a member of the Eric Roland Center for Neurodegenerative Diseases at the Hebrew University of Jerusalem.

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Goshen, I., Kreisel, T., Ben-Menachem-Zidon, O. et al. Brain interleukin-1 mediates chronic stress-induced depression in mice via adrenocortical activation and hippocampal neurogenesis suppression. Mol Psychiatry 13, 717–728 (2008). https://doi.org/10.1038/sj.mp.4002055

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