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Major Depression: A Role for Hippocampal Neurogenesis?

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Behavioral Neurobiology of Depression and Its Treatment

Part of the book series: Current Topics in Behavioral Neurosciences ((CTBN,volume 14))

Abstract

Since its discovery in mammals, adult neurogenesis, the process of generating functional neurons from neural progenitor cells in the adult brain, has inspired numerous animal studies. These have revealed that adult neurogenesis is a highly regulated phenomenon. Enriched environment, exercise and learning for instance, are positive regulators while stress and age are major negative regulators. Stressful life events are not only shown to reduce adult neurogenesis levels but are also discussed to be a key element in the development of various neuropsychiatric disorders such as depression. Interestingly, altered monoaminergic brain levels resulting from antidepressant treatment are shown to have a strong reinforcing effect on adult neurogenesis. Additionally, disturbed adult neurogenesis, possibly resulting in a malfunctioning hippocampus, may contribute to the cognitive deficits and reduced hippocampal volumes observed in depressed patients. Hence, the question arises as to whether disturbed adult neurogenesis and the etiopathogenesis of depression are causally linked. In this chapter, we discuss the possible causal interrelation of disturbed adult neurogenesis and the etiopathogenesis of depression as well as the possibility that adult neurogenesis is not exclusively linked to depression but is also linked to other psychiatric disorders including schizophrenia and neurodegenerative diseases like Alzheimer’s disease. Additionally, we look at the functional relevance of adult neurogenesis in different species, upon which we base our discussion as to whether adult neurogenesis could be causally linked to the development of certain brain disorders in humans, or whether it is only an epiphenomenon.

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References

  • Altman J (1962) Are new neurons formed in the brains of adult mammals? Science 135:1127–1128

    Article  PubMed  CAS  Google Scholar 

  • Altman J, Das GD (1965) Autoradiographic and histological evidence of postnatal hippocampal neurogenesis in rats. J Comp Neurol 124:319–335

    Article  PubMed  CAS  Google Scholar 

  • Altman J, Das GD (1967) Postnatal neurogenesis in the guinea-pig. Nature 214:1098–1101

    Article  PubMed  CAS  Google Scholar 

  • Amrein I, Isler K, Lipp HP (2011) Comparing adult hippocampal neurogenesis in mammalian species and orders: influence of chronological age and life history stage. Eur J Neurosci 34:978–987

    Article  PubMed  Google Scholar 

  • Anacker C, Zunszain PA, Cattaneo A, Carvalho LA, Garabedian MJ, Thuret S, Price J, Pariante CM (2011) Antidepressants increase human hippocampal neurogenesis by activating the glucocorticoid receptor. Mol Psychiatry 16:738–750

    Article  PubMed  CAS  Google Scholar 

  • Banasr M, Hery M, Printemps R, Daszuta A (2004) Serotonin-induced increases in adult cell proliferation and neurogenesis are mediated through different and common 5-HT receptor subtypes in the dentate gyrus and the subventricular zone. Neuropsychopharmacology 29:450–460

    Article  PubMed  CAS  Google Scholar 

  • Bannerman DM, Deacon RM, Offen S, Friswell J, Grubb M, Rawlins JN (2002) Double dissociation of function within the hippocampus: spatial memory and hyponeophagia. Behav Neurosci 116:884–901

    Article  PubMed  CAS  Google Scholar 

  • Barnea A, Nottebohm F (1996) Recruitment and replacement of hippocampal neurons in young and adult chickadees: an addition to the theory of hippocampal learning. Proc Natl Acad Sci U S A 93:714–718

    Article  PubMed  CAS  Google Scholar 

  • Bekinschtein P, Oomen CA, Saksida LM, Bussey TJ (2011) Effects of environmental enrichment and voluntary exercise on neurogenesis, learning and memory, and pattern separation: BDNF as a critical variable? Semin Cell Dev Biol 22:536–542

    Article  PubMed  CAS  Google Scholar 

  • Boekhoorn K, Joels M, Lucassen PJ (2006) Increased proliferation reflects glial and vascular-associated changes, but not neurogenesis in the presenile Alzheimer hippocampus. Neurobiol Dis 24:1–14

    Article  PubMed  CAS  Google Scholar 

  • Boldrini M, Arango V (2010) Antidepressants, age, and neuroprogenitors. Neuropsychopharmacology 35:351–352

    Article  PubMed  Google Scholar 

  • Boldrini M, Underwood MD, Hen R, Rosoklija GB, Dwork AJ, John Mann J, Arango V (2009) Antidepressants increase neural progenitor cells in the human hippocampus. Neuropsychopharmacology 34:2376–2389

    Article  PubMed  CAS  Google Scholar 

  • Bremner JD, Narayan M, Anderson ER, Staib LH, Miller HL, Charney DS (2000) Hippocampal volume reduction in major depression. Am J Psychiatry 157:115–118

    Article  PubMed  CAS  Google Scholar 

  • Brezun JM, Daszuta A (2000) Serotonin may stimulate granule cell proliferation in the adult hippocampus, as observed in rats grafted with foetal raphe neurons. Eur J Neurosci 12:391–396

    Article  PubMed  CAS  Google Scholar 

  • Broadbent NJ, Squire LR, Clark RE (2004) Spatial memory, recognition memory, and the hippocampus. Proc Natl Acad Sci U S A 101:14515–14520

    Article  PubMed  CAS  Google Scholar 

  • Burghardt NS, Park EH, Hen R, Fenton AA (2012) Adult-born hippocampal neurons promote cognitive flexibility in mice. Hippocampus 31(6):739–751

    Google Scholar 

  • Cahill L, McGaugh JL (1998) Mechanisms of emotional arousal and lasting declarative memory. Trends Neurosci 21:294–299

    Article  PubMed  CAS  Google Scholar 

  • Campbell S, Marriott M, Nahmias C, MacQueen GM (2004) Lower hippocampal volume in patients suffering from depression: a meta-analysis. Am J Psychiatry 161:598–607

    Article  PubMed  Google Scholar 

  • Caspi A, Sugden K, Moffitt TE, Taylor A, Craig IW, Harrington H, McClay J, Mill J, Martin J, Braithwaite A, Poulton R (2003) Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene. Science 301:386–389

    Article  PubMed  CAS  Google Scholar 

  • Chishti MA, Yang DS, Janus C, Phinney AL, Horne P, Pearson J, Strome R, Zuker N, Loukides J, French J, Turner S, Lozza G, Grilli M, Kunicki S, Morissette C, Paquette J, Gervais F, Bergeron C, Fraser PE, Carlson GA, George-Hyslop PS, Westaway D (2001) Early-onset amyloid deposition and cognitive deficits in transgenic mice expressing a double mutant form of amyloid precursor protein 695. J Biol Chem 276:21562–21570

    Article  PubMed  CAS  Google Scholar 

  • Clelland CD, Choi M, Romberg C, Clemenson GD Jr, Fragniere A, Tyers P, Jessberger S, Saksida LM, Barker RA, Gage FH, Bussey TJ (2009) A functional role for adult hippocampal neurogenesis in spatial pattern separation. Science 325:210–213

    Article  PubMed  CAS  Google Scholar 

  • Coras R, Siebzehnrubl FA, Pauli E, Huttner HB, Njunting M, Kobow K, Villmann C, Hahnen E, Neuhuber W, Weigel D, Buchfelder M, Stefan H, Beck H, Steindler DA, Blumcke I (2010) Low proliferation and differentiation capacities of adult hippocampal stem cells correlate with memory dysfunction in humans. Brain 133:3359–3372

    Article  PubMed  Google Scholar 

  • Crespel A, Rigau V, Coubes P, Rousset MC, de Bock F, Okano H, Baldy-Moulinier M, Bockaert J, Lerner-Natoli M (2005) Increased number of neural progenitors in human temporal lobe epilepsy. Neurobiol Dis 19:436–450

    Article  PubMed  CAS  Google Scholar 

  • Czeh B, Lucassen PJ (2007) What causes the hippocampal volume decrease in depression? Are neurogenesis, glial changes and apoptosis implicated? Eur Arch Psychiatry Clin Neurosci 257:250–260

    Article  PubMed  Google Scholar 

  • Czeh B, Michaelis T, Watanabe T, Frahm J, de Biurrun G, van Kampen M, Bartolomucci A, Fuchs E (2001) Stress-induced changes in cerebral metabolites, hippocampal volume, and cell proliferation are prevented by antidepressant treatment with tianeptine. Proc Natl Acad Sci U S A 98:12796–12801

    Article  PubMed  CAS  Google Scholar 

  • Czeh B, Welt T, Fischer AK, Erhardt A, Schmitt W, Muller MB, Toschi N, Fuchs E, Keck ME (2002) Chronic psychosocial stress and concomitant repetitive transcranial magnetic stimulation: effects on stress hormone levels and adult hippocampal neurogenesis. Biol Psychiatry 52:1057–1065

    Article  PubMed  CAS  Google Scholar 

  • Davachi L, Wagner AD (2002) Hippocampal contributions to episodic encoding: insights from relational and item-based learning. J Neurophysiol 88:982–990

    PubMed  Google Scholar 

  • Dawirs RR, Hildebrandt K, Teuchert-Noodt G (1998) Adult treatment with haloperidol increases dentate granule cell proliferation in the gerbil hippocampus. J Neural Transm 105:317–327

    Article  PubMed  CAS  Google Scholar 

  • Dayer AG, Ford AA, Cleaver KM, Yassaee M, Cameron HA (2003) Short-term and long-term survival of new neurons in the rat dentate gyrus. J Comp Neurol 460:563–572

    Article  PubMed  Google Scholar 

  • Deng W, Aimone JB, Gage FH (2010) New neurons and new memories: how does adult hippocampal neurogenesis affect learning and memory? Nat Rev Neurosci 11:339–350

    Article  PubMed  CAS  Google Scholar 

  • Deng W, Saxe MD, Gallina IS, Gage FH (2009) Adult-born hippocampal dentate granule cells undergoing maturation modulate learning and memory in the brain. J Neurosci 29:13532–13542

    Article  PubMed  CAS  Google Scholar 

  • Dias BG, Banerjee SB, Duman RS, Vaidya VA (2003) Differential regulation of brain derived neurotrophic factor transcripts by antidepressant treatments in the adult rat brain. Neuropharmacology 45:553–563

    Article  PubMed  CAS  Google Scholar 

  • Drapeau E, Mayo W, Aurousseau C, Le Moal M, Piazza PV, Abrous DN (2003) Spatial memory performances of aged rats in the water maze predict levels of hippocampal neurogenesis. Proc Natl Acad Sci U S A 100:14385–14390

    Article  PubMed  CAS  Google Scholar 

  • Dupret D, Fabre A, Dobrossy MD, Panatier A, Rodriguez JJ, Lamarque S, Lemaire V, Oliet SH, Piazza PV, Abrous DN (2007) Spatial learning depends on both the addition and removal of new hippocampal neurons. PLoS Biol 5:e214

    Article  PubMed  CAS  Google Scholar 

  • Dupret D, Revest JM, Koehl M, Ichas F, De Giorgi F, Costet P, Abrous DN, Piazza PV (2008) Spatial relational memory requires hippocampal adult neurogenesis. PLoS ONE 3:e1959

    Article  PubMed  CAS  Google Scholar 

  • Encinas JM, Vaahtokari A, Enikolopov G (2006) Fluoxetine targets early progenitor cells in the adult brain. Proc Natl Acad Sci U S A 103:8233–8238

    Article  PubMed  CAS  Google Scholar 

  • Eriksson PS, Perfilieva E, Bjork-Eriksson T, Alborn AM, Nordborg C, Peterson DA, Gage FH (1998) Neurogenesis in the adult human hippocampus. Nat Med 4:1313–1317

    Article  PubMed  CAS  Google Scholar 

  • Fahrner A, Kann G, Flubacher A, Heinrich C, Freiman TM, Zentner J, Frotscher M, Haas CA (2007) Granule cell dispersion is not accompanied by enhanced neurogenesis in temporal lobe epilepsy patients. Exp Neurol 203:320–332

    Article  PubMed  Google Scholar 

  • Fanselow MS, Dong HW (2010) Are the dorsal and ventral hippocampus functionally distinct structures? Neuron 65:7–19

    Article  PubMed  CAS  Google Scholar 

  • Frodl T, Jager M, Smajstrlova I, Born C, Bottlender R, Palladino T, Reiser M, Moller HJ, Meisenzahl EM (2008a) Effect of hippocampal and amygdala volumes on clinical outcomes in major depression: a 3-year prospective magnetic resonance imaging study. J Psychiatry Neurosci 33:423–430

    PubMed  Google Scholar 

  • Frodl TS, Koutsouleris N, Bottlender R, Born C, Jager M, Scupin I, Reiser M, Moller HJ, Meisenzahl EM (2008b) Depression-related variation in brain morphology over 3 years: effects of stress? Arch Gen Psychiatry 65:1156–1165

    Article  PubMed  Google Scholar 

  • Galea LA (2008) Gonadal hormone modulation of neurogenesis in the dentate gyrus of adult male and female rodents. Brain Res Rev 57:332–341

    Article  PubMed  CAS  Google Scholar 

  • Gaspar P, Cases O, Maroteaux L (2003) The developmental role of serotonin: news from mouse molecular genetics. Nat Rev Neurosci 4:1002–1012

    Article  PubMed  CAS  Google Scholar 

  • Gerdes J, Li L, Schlueter C, Duchrow M, Wohlenberg C, Gerlach C, Stahmer I, Kloth S, Brandt E, Flad HD (1991) Immunobiochemical and molecular biologic characterization of the cell proliferation-associated nuclear antigen that is defined by monoclonal antibody Ki-67. Am J Pathol 138:867–873

    PubMed  CAS  Google Scholar 

  • Geuze E, Vermetten E, Bremner JD (2005) MR-based in vivo hippocampal volumetrics: 2 Findings in neuropsychiatric disorders. Mol Psychiatry 10:160–184

    Article  PubMed  CAS  Google Scholar 

  • Glasper ER, Schoenfeld TJ, Gould E (2012) Adult neurogenesis: optimizing hippocampal function to suit the environment. Behav Brain Res 227:380–383

    Article  PubMed  Google Scholar 

  • Goldman SA, Nottebohm F (1983) Neuronal production, migration, and differentiation in a vocal control nucleus of the adult female canary brain. Proc Natl Acad Sci U S A 80:2390–2394

    Article  PubMed  CAS  Google Scholar 

  • Gould E (1999) Serotonin and hippocampal neurogenesis. Neuropsychopharmacology 21:46S–51S

    PubMed  CAS  Google Scholar 

  • Gould E, Beylin A, Tanapat P, Reeves A, Shors TJ (1999a) Learning enhances adult neurogenesis in the hippocampal formation. Nat Neurosci 2:260–265

    Article  PubMed  CAS  Google Scholar 

  • Gould E, Reeves AJ, Graziano MS, Gross CG (1999b) Neurogenesis in the neocortex of adult primates. Science 286:548–552

    Article  PubMed  CAS  Google Scholar 

  • Gould E, Tanapat P (1999) Stress and hippocampal neurogenesis. Biol Psychiatry 46:1472–1479

    Article  PubMed  CAS  Google Scholar 

  • Gould E, Tanapat P, McEwen BS, Flugge G, Fuchs E (1998) Proliferation of granule cell precursors in the dentate gyrus of adult monkeys is diminished by stress. Proc Natl Acad Sci U S A 95:3168–3171

    Article  PubMed  CAS  Google Scholar 

  • Grassi Zucconi G, Cipriani S, Balgkouranidou I, Scattoni R (2006) ‘One night’ sleep deprivation stimulates hippocampal neurogenesis. Brain Res Bull 69:375–381

    Article  PubMed  Google Scholar 

  • Gratzner HG (1982) Monoclonal antibody to 5-bromo- and 5-iododeoxyuridine: A new reagent for detection of DNA replication. Science 218:474–475

    Article  PubMed  CAS  Google Scholar 

  • Halim ND, Weickert CS, McClintock BW, Weinberger DR, Lipska BK (2004) Effects of chronic haloperidol and clozapine treatment on neurogenesis in the adult rat hippocampus. Neuropsychopharmacology 29:1063–1069

    Article  PubMed  CAS  Google Scholar 

  • Hanson ND, Owens MJ, Nemeroff CB (2011) Depression, antidepressants, and neurogenesis: a critical reappraisal. Neuropsychopharmacology 36:2589–2602

    Article  PubMed  Google Scholar 

  • Hellsten J, Wennstrom M, Mohapel P, Ekdahl CT, Bengzon J, Tingstrom A (2002) Electroconvulsive seizures increase hippocampal neurogenesis after chronic corticosterone treatment. Eur J Neurosci 16:283–290

    Article  PubMed  Google Scholar 

  • Henke PG (1990) Hippocampal pathway to the amygdala and stress ulcer development. Brain Res Bull 25:691–695

    Article  PubMed  CAS  Google Scholar 

  • Herman JP, Dolgas CM, Carlson SL (1998) Ventral subiculum regulates hypothalamo-pituitary-adrenocortical and behavioural responses to cognitive stressors. Neuroscience 86:449–459

    Article  PubMed  CAS  Google Scholar 

  • Herring A, Ambree O, Tomm M, Habermann H, Sachser N, Paulus W, Keyvani K (2009) Environmental enrichment enhances cellular plasticity in transgenic mice with Alzheimer-like pathology. Exp Neurol 216:184–192

    Article  PubMed  CAS  Google Scholar 

  • Heuser I, Yassouridis A, Holsboer F (1994) The combined dexamethasone/CRH test: a refined laboratory test for psychiatric disorders. J Psychiatr Res 28:341–356

    Article  PubMed  CAS  Google Scholar 

  • Holmes A (2008) Genetic variation in cortico-amygdala serotonin function and risk for stress-related disease. Neurosci Biobehav Rev 32:1293–1314

    Article  PubMed  CAS  Google Scholar 

  • Holsboer F (2001) Stress, hypercortisolism and corticosteroid receptors in depression: implications for therapy. J Affect Disord 62:77–91

    Article  PubMed  CAS  Google Scholar 

  • Honea R, Crow TJ, Passingham D, Mackay CE (2005) Regional deficits in brain volume in schizophrenia: a meta-analysis of voxel-based morphometry studies. Am J Psychiatry 162:2233–2245

    Article  PubMed  Google Scholar 

  • Imayoshi I, Sakamoto M, Ohtsuka T, Takao K, Miyakawa T, Yamaguchi M, Mori K, Ikeda T, Itohara S, Kageyama R (2008) Roles of continuous neurogenesis in the structural and functional integrity of the adult forebrain. Nat Neurosci 11:1153–1161

    Article  PubMed  CAS  Google Scholar 

  • Jacobs BL (2002) Adult brain neurogenesis and depression. Brain Behav Immun 16:602–609

    Article  PubMed  CAS  Google Scholar 

  • Jacobson L, Sapolsky R (1991) The role of the hippocampus in feedback regulation of the hypothalamic-pituitary-adrenocortical axis. Endocr Rev 12:118–134

    Article  PubMed  CAS  Google Scholar 

  • Jin K, Peel AL, Mao XO, Xie L, Cottrell BA, Henshall DC, Greenberg DA (2004) Increased hippocampal neurogenesis in Alzheimer’s disease. Proc Natl Acad Sci U S A 101:343–347

    Article  PubMed  CAS  Google Scholar 

  • Kee N, Sivalingam S, Boonstra R, Wojtowicz JM (2002) The utility of Ki-67 and BrdU as proliferative markers of adult neurogenesis. J Neurosci Methods 115:97–105

    Article  PubMed  CAS  Google Scholar 

  • Kempermann G (2002) Why new neurons? Possible functions for adult hippocampal neurogenesis. J Neurosci 22:635–638

    PubMed  CAS  Google Scholar 

  • Kempermann G (2008) The neurogenic reserve hypothesis: what is adult hippocampal neurogenesis good for? Trends Neurosci 31:163–169

    Article  PubMed  CAS  Google Scholar 

  • Kempermann G, Gage FH (1999) Experience-dependent regulation of adult hippocampal neurogenesis: effects of long-term stimulation and stimulus withdrawal. Hippocampus 9:321–332

    Article  PubMed  CAS  Google Scholar 

  • Kempermann G, Gast D, Gage FH (2002) Neuroplasticity in old age: sustained fivefold induction of hippocampal neurogenesis by long-term environmental enrichment. Ann Neurol 52:135–143

    Article  PubMed  Google Scholar 

  • Kempermann G, Jessberger S, Steiner B, Kronenberg G (2004) Milestones of neuronal development in the adult hippocampus. Trends Neurosci 27:447–452

    Article  PubMed  CAS  Google Scholar 

  • Kempermann G, Kuhn HG, Gage FH (1997) More hippocampal neurons in adult mice living in an enriched environment. Nature 386:493–495

    Article  PubMed  CAS  Google Scholar 

  • Kempermann G, Kuhn HG, Gage FH (1998) Experience-induced neurogenesis in the senescent dentate gyrus. J Neurosci 18:3206–3212

    PubMed  CAS  Google Scholar 

  • Kirby ED, Friedman AR, Covarrubias D, Ying C, Sun WG, Goosens KA, Sapolsky RM, Kaufer D (2012) Basolateral amygdala regulation of adult hippocampal neurogenesis and fear-related activation of newborn neurons. Mol Psychiatry 17:527–536

    Article  PubMed  CAS  Google Scholar 

  • Kitamura T, Saitoh Y, Takashima N, Murayama A, Niibori Y, Ageta H, Sekiguchi M, Sugiyama H, Inokuchi K (2009) Adult neurogenesis modulates the hippocampus-dependent period of associative fear memory. Cell 139:814–827

    Article  PubMed  CAS  Google Scholar 

  • Knoth R, Singec I, Ditter M, Pantazis G, Capetian P, Meyer RP, Horvat V, Volk B, Kempermann G (2010) Murine features of neurogenesis in the human hippocampus across the lifespan from 0 to 100 years. PLoS ONE 5:e8809

    Article  PubMed  CAS  Google Scholar 

  • Kobayashi K, Ikeda Y, Sakai A, Yamasaki N, Haneda E, Miyakawa T, Suzuki H (2010) Reversal of hippocampal neuronal maturation by serotonergic antidepressants. Proc Natl Acad Sci U S A 107:8434–8439

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Koolhaas JM, Bartolomucci A, Buwalda B, de Boer SF, Flugge G, Korte SM, Meerlo P, Murison R, Olivier B, Palanza P, Richter-Levin G, Sgoifo A, Steimer T, Stiedl O, van Dijk G, Wohr M, Fuchs E (2011) Stress revisited: a critical evaluation of the stress concept. Neurosci Biobehav Rev 35:1291–1301

    Article  PubMed  CAS  Google Scholar 

  • Kronenberg G, Bick-Sander A, Bunk E, Wolf C, Ehninger D, Kempermann G (2006) Physical exercise prevents age-related decline in precursor cell activity in the mouse dentate gyrus. Neurobiol Aging 27:1505–1513

    Article  PubMed  Google Scholar 

  • Kronenberg G, Kirste I, Inta D, Chourbaji S, Heuser I, Endres M, Gass P (2009) Reduced hippocampal neurogenesis in the GR (±) genetic mouse model of depression. Eur Arch Psychiatry Clin Neurosci 259:499–504

    Article  PubMed  Google Scholar 

  • Kuhn HG, Dickinson-Anson H, Gage FH (1996) Neurogenesis in the dentate gyrus of the adult rat: age-related decrease of neuronal progenitor proliferation. J Neurosci 16:2027–2033

    PubMed  CAS  Google Scholar 

  • Lanfumey L, Mongeau R, Cohen-Salmon C, Hamon M (2008) Corticosteroid-serotonin interactions in the neurobiological mechanisms of stress-related disorders. Neurosci Biobehav Rev 32:1174–1184

    Article  PubMed  CAS  Google Scholar 

  • Lee M, Olmes DG, Nietzer SL, Winnig M, Lesch KP, Schmitt AG (2010) Hippocampal neurogenesis during murine and human ontogenesis: same same but different?. FENS Abstr. vol 5, 011.39

    Google Scholar 

  • Lewejohann L, Reefmann N, Widmann P, Ambree O, Herring A, Keyvani K, Paulus W, Sachser N (2009) Transgenic Alzheimer mice in a semi-naturalistic environment: more plaques, yet not compromised in daily life. Behav Brain Res 201:99–102

    Article  PubMed  CAS  Google Scholar 

  • Lowry CA, Johnson PL, Hay-Schmidt A, Mikkelsen J, Shekhar A (2005) Modulation of anxiety circuits by serotonergic systems. Stress 8:233–246

    Article  PubMed  CAS  Google Scholar 

  • Lucassen PJ, Meerlo P, Naylor AS, van Dam AM, Dayer AG, Fuchs E, Oomen CA, Czeh B (2010a) Regulation of adult neurogenesis by stress, sleep disruption, exercise and inflammation: Implications for depression and antidepressant action. Eur Neuropsychopharmacol 20:1–17

    Article  PubMed  CAS  Google Scholar 

  • Lucassen PJ, Stumpel MW, Wang Q, Aronica E (2010b) Decreased numbers of progenitor cells but no response to antidepressant drugs in the hippocampus of elderly depressed patients. Neuropharmacology 58:940–949

    Article  PubMed  CAS  Google Scholar 

  • Lyons DM, Buckmaster PS, Lee AG, Wu C, Mitra R, Duffey LM, Buckmaster CL, Her S, Patel PD, Schatzberg AF (2010) Stress coping stimulates hippocampal neurogenesis in adult monkeys. Proc Natl Acad Sci U S A 107:14823–14827

    Article  PubMed  CAS  Google Scholar 

  • Madsen TM, Treschow A, Bengzon J, Bolwig TG, Lindvall O, Tingstrom A (2000) Increased neurogenesis in a model of electroconvulsive therapy. Biol Psychiatry 47:1043–1049

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Marlatt MW, Lucassen PJ (2010) Neurogenesis and Alzheimer’s disease: biology and pathophysiology in mice and men. Curr Alzheimer Res 7:113–125

    Article  PubMed  CAS  Google Scholar 

  • Maya Vetencourt JF, Sale A, Viegi A, Baroncelli L, De Pasquale R, O’Leary OF, Castren E, Maffei L (2008) The antidepressant fluoxetine restores plasticity in the adult visual cortex. Science 320:385–388

    Article  PubMed  CAS  Google Scholar 

  • Meshi D, Drew MR, Saxe M, Ansorge MS, David D, Santarelli L, Malapani C, Moore H, Hen R (2006) Hippocampal neurogenesis is not required for behavioral effects of environmental enrichment. Nat Neurosci 9:729–731

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Ming GL, Song H (2011) Adult neurogenesis in the mammalian brain: significant answers and significant questions. Neuron 70:687–702

    Article  PubMed  CAS  Google Scholar 

  • Mirescu C, Peters JD, Gould E (2004) Early life experience alters response of adult neurogenesis to stress. Nat Neurosci 7:841–846

    Article  PubMed  CAS  Google Scholar 

  • Moghaddam B, Bolinao ML, Stein-Behrens B, Sapolsky R (1994) Glucocorticoids mediate the stress-induced extracellular accumulation of glutamate. Brain Res 655:251–254

    Article  PubMed  CAS  Google Scholar 

  • Morris SA, Eaves DW, Smith AR, Nixon K (2010) Alcohol inhibition of neurogenesis: a mechanism of hippocampal neurodegeneration in an adolescent alcohol abuse model. Hippocampus 20:596–607

    PubMed  CAS  Google Scholar 

  • Moser MB, Moser EI (1998) Functional differentiation in the hippocampus. Hippocampus 8:608–619

    Article  PubMed  CAS  Google Scholar 

  • Moser MB, Moser EI, Forrest E, Andersen P, Morris RG (1995) Spatial learning with a minislab in the dorsal hippocampus. Proc Natl Acad Sci U S A 92:9697–9701

    Article  PubMed  CAS  Google Scholar 

  • Namba T, Mochizuki H, Onodera M, Mizuno Y, Namiki H, Seki T (2005) The fate of neural progenitor cells expressing astrocytic and radial glial markers in the postnatal rat dentate gyrus. Eur J Neurosci 22:1928–1941

    Article  PubMed  Google Scholar 

  • Namestkova K, Simonova Z, Sykova E (2005) Decreased proliferation in the adult rat hippocampus after exposure to the Morris water maze and its reversal by fluoxetine. Behav Brain Res 163:26–32

    Article  PubMed  CAS  Google Scholar 

  • Nibuya M, Morinobu S, Duman RS (1995) Regulation of BDNF and trkB mRNA in rat brain by chronic electroconvulsive seizure and antidepressant drug treatments. J Neurosci 15:7539–7547

    PubMed  CAS  Google Scholar 

  • Nilsson M, Perfilieva E, Johansson U, Orwar O, Eriksson PS (1999) Enriched environment increases neurogenesis in the adult rat dentate gyrus and improves spatial memory. J Neurobiol 39:569–578

    Article  PubMed  CAS  Google Scholar 

  • O`Keefe J, Nadel L (1978) The hippocampus as a cognitive map. Oxford University Press, Oxford

    Google Scholar 

  • Overstreet DH, Pucilowski O, Retton MC, Delagrange P, Guardiola-Lemaitre B (1998) Effects of melatonin receptor ligands on swim test immobility. NeuroReport 9:249–253

    Article  PubMed  CAS  Google Scholar 

  • Paizanis E, Hamon M, Lanfumey L (2007) Hippocampal neurogenesis, depressive disorders, and antidepressant therapy. Neural Plast 2007:73754

    Article  PubMed  Google Scholar 

  • Papp M, Gruca P, Boyer PA, Mocaer E (2003) Effect of agomelatine in the chronic mild stress model of depression in the rat. Neuropsychopharmacology 28:694–703

    Article  PubMed  CAS  Google Scholar 

  • Pariante CM, Lightman SL (2008) The HPA axis in major depression: classical theories and new developments. Trends Neurosci 31:464–468

    Article  PubMed  CAS  Google Scholar 

  • Perera TD, Coplan JD, Lisanby SH, Lipira CM, Arif M, Carpio C, Spitzer G, Santarelli L, Scharf B, Hen R, Rosoklija G, Sackeim HA, Dwork AJ (2007) Antidepressant-induced neurogenesis in the hippocampus of adult nonhuman primates. J Neurosci 27:4894–4901

    Article  PubMed  CAS  Google Scholar 

  • Pham K, McEwen BS, Ledoux JE, Nader K (2005) Fear learning transiently impairs hippocampal cell proliferation. Neuroscience 130:17–24

    Article  PubMed  CAS  Google Scholar 

  • Pittenger C, Duman RS (2008) Stress, depression, and neuroplasticity: a convergence of mechanisms. Neuropsychopharmacology 33:88–109

    Article  PubMed  CAS  Google Scholar 

  • Pollak DD, Monje FJ, Zuckerman L, Denny CA, Drew MR, Kandel ER (2008) An animal model of a behavioral intervention for depression. Neuron 60:149–161

    Article  PubMed  CAS  Google Scholar 

  • Ramirez-Amaya V, Marrone DF, Gage FH, Worley PF, Barnes CA (2006) Integration of new neurons into functional neural networks. J Neurosci 26:12237–12241

    Article  PubMed  CAS  Google Scholar 

  • Ramirez-Rodriguez G, Klempin F, Babu H, Benitez-King G, Kempermann G (2009) Melatonin modulates cell survival of new neurons in the hippocampus of adult mice. Neuropsychopharmacology 34:2180–2191

    Article  PubMed  CAS  Google Scholar 

  • Reif A, Fritzen S, Finger M, Strobel A, Lauer M, Schmitt A, Lesch KP (2006) Neural stem cell proliferation is decreased in schizophrenia, but not in depression. Mol Psychiatry 11:514–522

    Article  PubMed  CAS  Google Scholar 

  • Reif A, Schmitt A, Fritzen S, Lesch KP (2007) Neurogenesis and schizophrenia: dividing neurons in a divided mind? Eur Arch Psychiatry Clin Neurosci 257:290–299

    Article  PubMed  Google Scholar 

  • Revest JM, Dupret D, Koehl M, Funk-Reiter C, Grosjean N, Piazza PV, Abrous DN (2009) Adult hippocampal neurogenesis is involved in anxiety-related behaviors. Mol Psychiatry 14:959–967

    Article  PubMed  Google Scholar 

  • Ridder S, Chourbaji S, Hellweg R, Urani A, Zacher C, Schmid W, Zink M, Hortnagl H, Flor H, Henn FA, Schutz G, Gass P (2005) Mice with genetically altered glucocorticoid receptor expression show altered sensitivity for stress-induced depressive reactions. J Neurosci 25:6243–6250

    Article  PubMed  CAS  Google Scholar 

  • Sahay A, Hen R (2007) Adult hippocampal neurogenesis in depression. Nat Neurosci 10:1110–1115

    Article  PubMed  CAS  Google Scholar 

  • Sahay A, Scobie KN, Hill AS, O’Carroll CM, Kheirbek MA, Burghardt NS, Fenton AA, Dranovsky A, Hen R (2011) Increasing adult hippocampal neurogenesis is sufficient to improve pattern separation. Nature 472:466–470

    Article  PubMed  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

    Article  PubMed  CAS  Google Scholar 

  • Saveanu RV, Nemeroff CB (2012) Etiology of depression: genetic and environmental factors. Psychiatr Clin North Am 35:51–71

    Article  PubMed  Google Scholar 

  • Saxe MD, Battaglia F, Wang JW, Malleret G, David DJ, Monckton JE, Garcia AD, Sofroniew MV, Kandel ER, Santarelli L, Hen R, Drew MR (2006) Ablation of hippocampal neurogenesis impairs contextual fear conditioning and synaptic plasticity in the dentate gyrus. Proc Natl Acad Sci U S A 103:17501–17506

    Article  PubMed  CAS  Google Scholar 

  • Schloesser RJ, Lehmann M, Martinowich K, Manji HK, Herkenham M (2010) Environmental enrichment requires adult neurogenesis to facilitate the recovery from psychosocial stress. Mol Psychiatry 15:1152–1163

    Article  PubMed  CAS  Google Scholar 

  • Schmitt A, Weber S, Jatzko A, Braus DF, Henn FA (2004) Hippocampal volume and cell proliferation after acute and chronic clozapine or haloperidol treatment. J Neural Transm 111:91–100

    Article  PubMed  CAS  Google Scholar 

  • Scholzen T, Gerdes J (2000) The Ki-67 protein: from the known and the unknown. J Cell Physiol 182:311–322

    Article  PubMed  CAS  Google Scholar 

  • Segal M, Richter-Levin G, Maggio N (2010) Stress-induced dynamic routing of hippocampal connectivity: a hypothesis. Hippocampus 20:1332–1338

    Article  PubMed  Google Scholar 

  • Seki T, Arai Y (1995) Age-related production of new granule cells in the adult dentate gyrus. NeuroReport 6:2479–2482

    Article  PubMed  CAS  Google Scholar 

  • Sheline YI (1996) Hippocampal atrophy in major depression: a result of depression-induced neurotoxicity? Mol Psychiatry 1:298–299

    PubMed  CAS  Google Scholar 

  • Smith ME (2005) Bilateral hippocampal volume reduction in adults with post-traumatic stress disorder: a meta-analysis of structural MRI studies. Hippocampus 15:798–807

    Article  PubMed  Google Scholar 

  • Snyder JS, Cameron HA (2012) Could adult hippocampal neurogenesis be relevant for human behavior? Behav Brain Res 227:384–390

    Article  PubMed  Google Scholar 

  • Snyder JS, Soumier A, Brewer M, Pickel J, Cameron HA (2011) Adult hippocampal neurogenesis buffers stress responses and depressive behaviour. Nature 476:458–461

    Article  PubMed  CAS  Google Scholar 

  • Spritzer MD, Galea LA (2007) Testosterone and dihydrotestosterone, but not estradiol, enhance survival of new hippocampal neurons in adult male rats. Dev Neurobiol 67:1321–1333

    Article  PubMed  CAS  Google Scholar 

  • Spritzer MD, Ibler E, Inglis W, Curtis MG (2011) Testosterone and social isolation influence adult neurogenesis in the dentate gyrus of male rats. Neuroscience 195:180–190

    Article  PubMed  CAS  Google Scholar 

  • Squire LR, Knowlton B, Musen G (1993) The structure and organization of memory. Annu Rev Psychol 44:453–495

    Article  PubMed  CAS  Google Scholar 

  • Squire LR, Ojemann JG, Miezin FM, Petersen SE, Videen TO, Raichle ME (1992) Activation of the hippocampus in normal humans: a functional anatomical study of memory. Proc Natl Acad Sci U S A 89:1837–1841

    Article  PubMed  CAS  Google Scholar 

  • Steen RG, Mull C, McClure R, Hamer RM, Lieberman JA (2006) Brain volume in first-episode schizophrenia: systematic review and meta-analysis of magnetic resonance imaging studies. Br J Psychiatry 188:510–518

    Article  PubMed  Google Scholar 

  • Stockmeier CA, Mahajan GJ, Konick LC, Overholser JC, Jurjus GJ, Meltzer HY, Uylings HB, Friedman L, Rajkowska G (2004) Cellular changes in the postmortem hippocampus in major depression. Biol Psychiatry 56:640–650

    Article  PubMed  Google Scholar 

  • Swanson LW, Cowan WM (1977) An autoradiographic study of the organization of the efferent connections of the hippocampal formation in the rat. J Comp Neurol 172:49–84

    Article  PubMed  CAS  Google Scholar 

  • Tanapat P, Hastings NB, Reeves AJ, Gould E (1999) Estrogen stimulates a transient increase in the number of new neurons in the dentate gyrus of the adult female rat. J Neurosci 19:5792–5801

    PubMed  CAS  Google Scholar 

  • Tata DA, Anderson BJ (2010) The effects of chronic glucocorticoid exposure on dendritic length, synapse numbers and glial volume in animal models: implications for hippocampal volume reductions in depression. Physiol Behav 99:186–193

    Article  PubMed  CAS  Google Scholar 

  • Tata DA, Marciano VA, Anderson BJ (2006) Synapse loss from chronically elevated glucocorticoids: relationship to neuropil volume and cell number in hippocampal area CA3. J Comp Neurol 498:363–374

    Article  PubMed  CAS  Google Scholar 

  • Taupin P (2010) A dual activity of ROS and oxidative stress on adult neurogenesis and Alzheimer’s disease. Cent Nerv Syst Agents Med Chem 10:16–21

    Article  PubMed  CAS  Google Scholar 

  • Teicher MH, Anderson CM, Polcari A (2012) Childhood maltreatment is associated with reduced volume in the hippocampal subfields CA3, dentate gyrus, and subiculum. Proc Natl Acad Sci U S A 109:E563–E572

    Article  PubMed  CAS  Google Scholar 

  • Thomas RM, Hotsenpiller G, Peterson DA (2007) Acute psychosocial stress reduces cell survival in adult hippocampal neurogenesis without altering proliferation. J Neurosci 27:2734–2743

    Article  PubMed  CAS  Google Scholar 

  • van Groen T, Wyss JM (1990) Extrinsic projections from area CA1 of the rat hippocampus: olfactory, cortical, subcortical, and bilateral hippocampal formation projections. J Comp Neurol 302:515–528

    Article  PubMed  Google Scholar 

  • van Os J, Kenis G, Rutten BP (2010) The environment and schizophrenia. Nature 468:203–212

    Article  PubMed  CAS  Google Scholar 

  • van Praag H, Christie BR, Sejnowski TJ, Gage FH (1999) Running enhances neurogenesis, learning, and long-term potentiation in mice. Proc Natl Acad Sci U S A 96:13427–13431

    Article  PubMed  Google Scholar 

  • van Praag H, Shubert T, Zhao C, Gage FH (2005) Exercise enhances learning and hippocampal neurogenesis in aged mice. J Neurosci 25:8680–8685

    Article  PubMed  CAS  Google Scholar 

  • van Praag HM (2004) Can stress cause depression? Prog Neuropsychopharmacol Biol Psychiatry 28:891–907

    Article  PubMed  CAS  Google Scholar 

  • Veena J, Srikumar BN, Raju TR, Shankaranarayana Rao BS (2009) Exposure to enriched environment restores the survival and differentiation of new born cells in the hippocampus and ameliorates depressive symptoms in chronically stressed rats. Neurosci Lett 455:178–182

    Article  PubMed  CAS  Google Scholar 

  • Videbech P, Ravnkilde B (2004) Hippocampal volume and depression: a meta-analysis of MRI studies. Am J Psychiatry 161:1957–1966

    Article  PubMed  Google Scholar 

  • von Bohlen and Halbach O (2011) Immunohistological markers for proliferative events, gliogenesis, and neurogenesis within the adult hippocampus. Cell Tissue Res 345:1–19

    Google Scholar 

  • Wahlberg KE, Wynne LC, Oja H, Keskitalo P, Pykalainen L, Lahti I, Moring J, Naarala M, Sorri A, Seitamaa M, Laksy K, Kolassa J, Tienari P (1997) Gene-environment interaction in vulnerability to schizophrenia: findings from the finnish adoptive family study of Schizophrenia. Am J Psychiatry 154:355–362

    PubMed  CAS  Google Scholar 

  • Wakade CG, Mahadik SP, Waller JL, Chiu FC (2002) Atypical neuroleptics stimulate neurogenesis in adult rat brain. J Neurosci Res 69:72–79

    Article  PubMed  CAS  Google Scholar 

  • Wang HD, Dunnavant FD, Jarman T, Deutch AY (2004) Effects of antipsychotic drugs on neurogenesis in the forebrain of the adult rat. Neuropsychopharmacology 29:1230–1238

    Article  PubMed  CAS  Google Scholar 

  • Watson DR, Bai F, Barrett SL, Turkington A, Rushe TM, Mulholland CC, Cooper SJ (2012) Structural changes in the hippocampus and amygdala at first episode of psychosis. Brain Imaging Behav 6:49–60

    Article  PubMed  Google Scholar 

  • West MJ, Gundersen HJ (1990) Unbiased stereological estimation of the number of neurons in the human hippocampus. J Comp Neurol 296:1–22

    Article  PubMed  CAS  Google Scholar 

  • Zhang CL, Zou Y, He W, Gage FH, Evans RM (2008) A role for adult TLX-positive neural stem cells in learning and behaviour. Nature 451:1004–1007

    Article  PubMed  CAS  Google Scholar 

  • Zigova T, Pencea V, Wiegand SJ, Luskin MB (1998) Intraventricular administration of BDNF increases the number of newly generated neurons in the adult olfactory bulb. Mol Cell Neurosci 11:234–245

    Article  PubMed  CAS  Google Scholar 

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Lee, M.M., Reif, A., Schmitt, A.G. (2012). Major Depression: A Role for Hippocampal Neurogenesis?. In: Cowen, P., Sharp, T., Lau, J. (eds) Behavioral Neurobiology of Depression and Its Treatment. Current Topics in Behavioral Neurosciences, vol 14. Springer, Berlin, Heidelberg. https://doi.org/10.1007/7854_2012_226

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