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Neurogenesis and depression: what animal models tell us about the link

Abstract

There is growing evidence that stress causes a decrease of neurogenesis in the dentate gyrus and antidepressant treatment in turn stimulates the cell proliferation in the dentate gyrus. This has led to the hypothesis that a decreased neurogenesis might be linked to the pathophysiology of major depression. The article reviews the relationship of depressive-like behavior and neurogenesis in three animal models of depression with high validity: learned helplessness, chronic mild stress and chronic psychosocial stress of the tree shrew. All animal models provide evidence that stress which can lead to depressive-like behavior, in parallel causes a decrease of neurogenesis; vice versa, antidepressant treatment is able to revert not only behavioral changes but also to normalize neurogenesis. But the animal models argue against the notion that decreases of neurogenesis are the cause or the consequence of depressive-like behavior since depressive-like behavior can occur without impairments in neurogenesis and decreasing neurogenesis does not neccessarily lead to depressive-like behavior. This suggests that neurogenesis does not directly control affect but is tightly connected to the modulation of affect by stress and antidepressant measures.

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References

  • Aimone JB, Wiles J, Gage FH (2006) Potential role for adult neurogenesis in the encoding of time in new memories. Nat Neurosci 9:723–727

    PubMed  Article  CAS  Google Scholar 

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

    PubMed  Article  CAS  Google Scholar 

  • Amat J, Baratta MV, Paul E, Bland ST, Watkins LR, Maier SF (2005) Medial prefrontal cortex determines how stressor controllability affects behavior and dorsal raphe nucleus. Nat Neurosci 8:365–371

    PubMed  Article  CAS  Google Scholar 

  • Dranovsky A, Hen R (2006) Hippocampal neurogenesis: regulation by stress and antidepressants. Biol Psychiatry 59:1136–1143

    PubMed  Article  CAS  Google Scholar 

  • Duman RS, Monteggia LM (2006) A neurotrophic model for stress-related mood disorders. Biol Psychiatry 59:1116–1127

    PubMed  Article  CAS  Google Scholar 

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

    PubMed  Article  CAS  Google Scholar 

  • Fuchs E, Flügge G (2002) Social stress in tree shrews: effects on physiology, brain function, and behavior of subordinate individuals. Pharmacol Biochem Behav 73:247–258

    PubMed  Article  CAS  Google Scholar 

  • Gage FH (2002) Neurogenesis in the adult brain. J Neurosci 22:612–613

    PubMed  CAS  Google Scholar 

  • Goldapple K, Segal Z, Garson C, Lau M, Bieling P, Kennedy S, Mayberg H (2004) Modulation of cortical-limbic pathways in major depression: treatment-specific effects of cognitive behavior therapy. Arch Gen Psychiatry 61:34–41

    PubMed  Article  Google Scholar 

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

    PubMed  Article  CAS  Google Scholar 

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

    PubMed  Article  CAS  Google Scholar 

  • Henn FA, Vollmayr B (2004) Neurogenesis and depression: etiology or epiphenomenon? Biol Psychiatry 56:146–150

    PubMed  Article  Google Scholar 

  • Kendler KS, Hettema JM, Butera F, Gardner CO, Prescott CA (2003) Life event dimensions of loss, humiliation, entrapment, and danger in the prediction of onsets of major depression and generalized anxiety. Arch Gen Psychiatry 60:789–796

    PubMed  Article  Google Scholar 

  • Lee KJ, Kim SJ, Kim SW, Choi SH, Shin YC, Park SH, Moon BH, Cho E, Lee MS, Choi SH, Chun BG, Shin KH (2006) Chronic mild stress decreases survival, but not proliferation, of new-born cells in adult rat hippocampus. Exp Mol Med 28:44–54

    Google Scholar 

  • Leuner B, Gould E, Shors TJ (2006) Is there a link between adult neurogenesis and learning? Hippocampus 16:216–224

    PubMed  Article  Google Scholar 

  • Malberg JE, Duman RS (2003) Cell proliferation in adult hippocampus is decreased by inescapable stress: reversal by fluoxetine treatment. Neuropsychopharmacology 28:1562–1571

    PubMed  Article  CAS  Google Scholar 

  • Ming GL, Song H (2005) Adult neurogenesis in the mammalian central nervous system. Annu Rev Neurosci 28:223–250

    PubMed  Article  CAS  Google Scholar 

  • Palmer TD, Willhoite AR, Gage FH (2000) Vascular niche for adult hippocampal neurogenesis. J Comp Neurol 425:479–494

    PubMed  Article  CAS  Google Scholar 

  • Santarelli L, Saxe M, Gross C, Surget A, Battaglia F, Dulawa S, Weisstaub N, Lee J, Duman R, Arancio O, Belzung C, Hen R (2003) Requirement of hippocampal neurogenesis for the behavioral effects of antidepressants. Science 301:805–809

    PubMed  Article  CAS  Google Scholar 

  • Vollmayr B, Henn FA (2003) Stress models of depression. Clin Neurosci Res 3:245–251

    Article  Google Scholar 

  • Vollmayr B, Simonis C, Weber S, Gass P, Henn FA (2003) Reduced cell proliferation in the dentate gyrus is not correlated with the development of learned helplessness. Biol Psychiatry 54:1035–1040

    PubMed  Article  Google Scholar 

  • Willner P, Muscat R, Papp M (1992) Chronic mild stress-induced anhedonia: a realistic animal model of depression. Neurosci Biobehav Rev 16:525–534

    PubMed  Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Wiskott L, Rasch MJ, Kempermann G (2006) A functional hypothesis for adult hippocampal neurogenesis: avoidance of catastrophic interference in the dentate gyrus. Hippocampus 16:329–343

    PubMed  Article  Google Scholar 

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Correspondence to Barbara Vollmayr.

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Vollmayr, B., Mahlstedt, M.M. & Henn, F.A. Neurogenesis and depression: what animal models tell us about the link. Eur Arch Psychiatry Clin Neurosc 257, 300–303 (2007). https://doi.org/10.1007/s00406-007-0734-2

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  • DOI: https://doi.org/10.1007/s00406-007-0734-2

Keywords

  • learned helplessness
  • animal model
  • depression
  • neurogenesis