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Stress, hippocampal neurogenesis and cognition: functional correlations

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Frontiers in Biology

Abstract

The brain of many species including humans, harbors stem cells that continue to generate new neurons up into adulthood. This form of structural plasticity occurs in a limited number of brain regions, i.e. the subventricular zone and the hippocampal dentate gyrus and is regulated by environmental and hormonal factors. In this minireview, we provide an overview of the effects of stress and glucocorticoid hormones on adult hippocampal neurogenesis and discuss how these effects may be relevant for cognitive function and possibly, brain disease. While its exact functional role remains elusive, adult neurogenesis has been implicated in learning and memory, fear and mood regulation and recently, adult-born neurons were found to be involved in specific cognitive functions such as pattern separation (i.e. the ability to form unique memory representations) and cognitive flexibility. The process of adult neurogenesis is influenced by several factors; whereas e.g. exercise stimulates, exposure to stress and stress hormones generally inhibit neurogenesis. Effects of acute, mild stress are generally short-lasting and recover quickly, but chronic or severe forms of stress can induce lasting reductions in adult neurogenesis. Some of the inhibitory effects of stress can be rescued by exercise, by allowing a period of recovery from stress, by drugs that target the stress system, or by some, but not all, antidepressants. Stress may, partly through its effects on adult neurogenesis, alter structure and plasticity of the hippocampal circuit. This can lead to subsequent changes in stress responsivity and aspects of memory processing, which may be particularly relevant for stress related psychopathology or brain diseases that involve perturbed memory processing.

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References

  • Abrous D N, Koehl M, Le Moal M (2005). Adult neurogenesis: from precursors to network and physiology. Physiol Rev, 85(2): 523–569

    Article  CAS  PubMed  Google Scholar 

  • Aimone J B, Deng W, Gage F H (2010). Adult neurogenesis: integrating theories and separating functions. Trends Cogn Sci, 14(7): 325–337

    Article  PubMed  PubMed Central  Google Scholar 

  • Aimone J B, Wiles J, Gage F H (2009). Computational influence of adult neurogenesis on memory encoding. Neuron, 61(2): 187–202

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Alonso R, Griebel G, Pavone G, Stemmelin J, Le Fur G, Soubrié P (2004). Blockade of CRF(1) or V(1b) receptors reverses stressinduced suppression of neurogenesis in a mouse model of depression. Mol Psychiatry, 9(3): 278–286, 224

    Article  CAS  PubMed  Google Scholar 

  • Anacker C, Cattaneo A, Luoni A, Musaelyan K, Zunszain P A, Milanesi E, Rybka J, Berry A, Cirulli F, Thuret S, Price J, Riva M A, Gennarelli M, Pariante CM (2013). Glucocorticoid-related molecular signaling pathways regulating hippocampal neurogenesis. Neuropsychopharmacology, 38(5): 872–883

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Arruda-Carvalho M, Sakaguchi M, Akers K G, Josselyn S A, Frankland P W (2011). Posttraining ablation of adult-generated neurons degrades previously acquired memories. J Neurosci, 31(42): 15113–15127

    Article  CAS  PubMed  Google Scholar 

  • Balu D T, Lucki I (2009). Adult hippocampal neurogenesis: regulation, functional implications, and contribution to disease pathology. Neurosci Biobehav Rev, 33(3): 232–252

    Article  PubMed  Google Scholar 

  • Banasr M, Duman R S (2007). Regulation of neurogenesis and gliogenesis by stress and antidepressant treatment. CNS Neurol Disord Drug Targets, 6(5): 311–320

    Article  CAS  PubMed  Google Scholar 

  • Becker S (2005). A computational principle for hippocampal learning and neurogenesis. Hippocampus, 15(6): 722–738

    Article  PubMed  Google Scholar 

  • Bekinschtein P, Kent B A, Oomen C A, Clemenson G D, Gage F H, Saksida L M, Bussey T J (2014). Brain-derived neurotrophic factor interacts with adult-born immature cells in the dentate gyrus during consolidation of overlapping memories. Hippocampus, 24(8): 905–911

    Article  PubMed  PubMed Central  Google Scholar 

  • Bekinschtein P, Kent B A, Oomen C A, Clemenson G D, Jr., Gage F H, Saksida L M, Bussey T J (2013). BDNF in the Dentate Gyrus Is Required for Consolidation of “Pattern-Separated” Memories. Cell Reports, 5: 1–10

    Article  CAS  Google Scholar 

  • Bekinschtein P, Oomen C A, Saksida L M, Bussey T J (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(5): 536–542

    Article  CAS  PubMed  Google Scholar 

  • Ben Abdallah N M, Filipkowski R K, Pruschy M, Jaholkowski P, Winkler J, Kaczmarek L, Lipp H P (2013). Impaired long-term memory retention: common denominator for acutely or genetically reduced hippocampal neurogenesis in adult mice. Behav Brain Res, 252: 275–286

    Article  PubMed  Google Scholar 

  • Besnard A, Sahay A (2016). Adult Hippocampal Neurogenesis, Fear Generalization, and Stress. Neuropsychopharmacology, 41(1): 24–44

    Article  PubMed  Google Scholar 

  • Binder E B, Bradley R G, Liu W, Epstein MP, Deveau T C, Mercer K B, Tang Y, Gillespie C F, Heim C M, Nemeroff C B, Schwartz A C, Cubells J F, Ressler K J (2008). Association of FKBP5 polymorphisms and childhood abuse with risk of posttraumatic stress disorder symptoms in adults. JAMA, 299(11): 1291–1305

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Boku S, Toda H, Nakagawa S, Kato A, Inoue T, Koyama T, Hiroi N, Kusumi I (2015). Neonatal maternal separation alters the capacity of adult neural precursor cells to differentiate into neurons via methylation of retinoic acid receptor gene promoter. Biol Psychiatry, 77(4): 335–344

    Article  CAS  PubMed  Google Scholar 

  • Bruel-Jungerman E, Lucassen P J, Francis F (2011). Cholinergic influences on cortical development and adult neurogenesis. Behav Brain Res, 221(2): 379–388

    Article  CAS  PubMed  Google Scholar 

  • Burghardt N S, Park E H, Hen R, Fenton A A (2012). Adult-born hippocampal neurons promote cognitive flexibility in mice. Hippocampus, 22(9): 1795–1808

    Article  PubMed  PubMed Central  Google Scholar 

  • Chetty S, Friedman A R, Taravosh-Lahn K, Kirby E D, Mirescu C, Guo F, Krupik D, Nicholas A, Geraghty A C, Krishnamurthy A, Tsai MK, Covarrubias D, Wong A T, Francis D D, Sapolsky R M, Palmer T D, Pleasure D, Kaufer D (2014). Stress and glucocorticoids promote oligodendrogenesis in the adult hippocampus. Mol Psychiatry, 19 (12): 1275–1283

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Clelland C D, Choi M, Romberg C, Clemenson G D, Fragniere A, Tyers P, Jessberger S, Saksida L M, Barker R A, Gage F H, Bussey T J (2009). A functional role for adult hippocampal neurogenesis in spatial pattern separation. Science, 325(5937): 210–213

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Creer D J, Romberg C, Saksida L M, van Praag H, Bussey T J (2010). Running enhances spatial pattern separation in mice. Proc Natl Acad Sci USA, 107(5): 2367–2372

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Czéh B, Lucassen P J (2007). What causes the hippocampal volume decrease in depression? Are neurogenesis, glial changes and apoptosis implicated? Eur Arch Psychiatry Clin Neurosci, 257(5): 250–260

    Article  PubMed  Google Scholar 

  • Czéh B, Simon M, Schmelting B, Hiemke C, Fuchs E (2006). Astroglial plasticity in the hippocampus is affected by chronic psychosocial stress and concomitant fluoxetine treatment. Neuropsychopharmacology, 31(8): 1616–1626

    Article  PubMed  CAS  Google Scholar 

  • Czéh B, Welt T, Fischer A K, Erhardt A, Schmitt W, Müller MB, Toschi N, Fuchs E, Keck M E (2002). Chronic psychosocial stress and concomitant repetitive transcranial magnetic stimulation: effects on stress hormone levels and adult hippocampal neurogenesis. Biol Psychiatry, 52(11): 1057–1065

    Article  PubMed  Google Scholar 

  • Dagyte G, van der Zee E A, Postema F, Luiten P G, Den Boer J A, Trentani A, Meerlo P (2009). Chronic but not acute foot-shock stress leads to temporary suppression of cell proliferation in rat hippocampus. Neuroscience, 162(4): 904–913

    Article  CAS  PubMed  Google Scholar 

  • Datson N A, Speksnijder N, Mayer J L, Steenbergen P J, Korobko O, Goeman J, de Kloet E R, Joëls M, Lucassen P J (2012). The transcriptional response to chronic stress and glucocorticoid receptor blockade in the hippocampal dentate gyrus. Hippocampus, 22(2): 359–371

    Article  CAS  PubMed  Google Scholar 

  • de Kloet E R, Joëls M, Holsboer F (2005). Stress and the brain: from adaptation to disease. Nat Rev Neurosci, 6(6): 463–475

    Article  PubMed  CAS  Google Scholar 

  • Djavadian R L (2004). Serotonin and neurogenesis in the hippocampal dentate gyrus of adult mammals. Acta Neurobiol Exp (Wars), 64(2): 189–200

    Google Scholar 

  • Domínguez-Escribà L, Hernández-Rabaza V, Soriano-Navarro M, Barcia J A, Romero F J, García-Verdugo J M, Canales J J (2006). Chronic cocaine exposure impairs progenitor proliferation but spares survival and maturation of neural precursors in adult rat dentate gyrus. Eur J Neurosci, 24(2): 586–594

    Article  PubMed  Google Scholar 

  • Dranovsky A, Hen R (2006). Hippocampal neurogenesis: regulation by stress and antidepressants. Biol Psychiatry, 59(12): 1136–1143

    Article  CAS  PubMed  Google Scholar 

  • Droste S K, Gesing A, Ulbricht S, Müller M B, Linthorst A C, Reul J M (2003). Effects of long-term voluntary exercise on the mouse hypothalamic-pituitary-adrenocortical axis. Endocrinology, 144(7): 3012–3023

    Article  CAS  PubMed  Google Scholar 

  • Ehninger D, Kempermann G (2006). Paradoxical effects of learning the Morris water maze on adult hippocampal neurogenesis in mice may be explained by a combination of stress and physical activity. Genes Brain Behav, 5(1): 29–39

    Article  CAS  PubMed  Google Scholar 

  • Erdmann G, Berger S, Schütz G (2008). Genetic dissection of glucocorticoid receptor function in the mouse brain. J Neuroendocrinol, 20(6): 655–659

    Article  CAS  PubMed  Google Scholar 

  • Fitzsimons C P, Herbert J, Schouten M, Meijer O C, Lucassen P J, Lightman S (2016). Circadian and Ultradian Glucocorticoid Rhythmicity: Implications for the Effects of Glucocorticoids on Neural Stem Cells and Adult Hippocampal Neurogenesis. Front Neuroendocrinol, (In press)

    Google Scholar 

  • Fitzsimons C P, van Hooijdonk L W, Schouten M, Zalachoras I, Brinks V, Zheng T, Schouten T G, Saaltink D J, Dijkmans T, Steindler D A, Verhaagen J, Verbeek F J, Lucassen P J, de Kloet E R, Meijer O C, Karst H, Joels M, Oitzl M S, Vreugdenhil E (2013). Knockdown of the glucocorticoid receptor alters functional integration of newborn neurons in the adult hippocampus and impairs fear-motivated behavior. Mol Psychiatry, 18(9): 993–1005

    Article  CAS  PubMed  Google Scholar 

  • Galea L A (2008). Gonadal hormone modulation of neurogenesis in the dentate gyrus of adult male and female rodents. Brain Res Brain Res Rev, 57(2): 332–341

    Article  CAS  Google Scholar 

  • Garcia A, Steiner B, Kronenberg G, Bick-Sander A, Kempermann G (2004). Age-dependent expression of glucocorticoid- and mineralocorticoid receptors on neural precursor cell populations in the adult murine hippocampus. Aging Cell, 3(6): 363–371

    Article  CAS  PubMed  Google Scholar 

  • Garthe A, Behr J, Kempermann G (2009). Adult-generated hippocampal neurons allow the flexible use of spatially precise learning strategies. PLoS ONE, 4 (5): e5464

    Article  CAS  Google Scholar 

  • Garthe A, Huang Z, Kaczmarek L, Filipkowski R K, Kempermann G (2014). Not all water mazes are created equal: cyclin D2 knockout mice with constitutively suppressed adult hippocampal neurogenesis do show specific spatial learning deficits. Genes Brain Behav, 13(4): 357–364

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ge S, Yang C H, Hsu K S, Ming G L, Song H (2007). A critical period for enhanced synaptic plasticity in newly generated neurons of the adult brain. Neuron, 54(4): 559–566

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gould E (2007). How widespread is adult neurogenesis in mammals? Nat Rev Neurosci, 8(6): 481–488

  • Gould E, Beylin A, Tanapat P, Reeves A, Shors T J (1999). Learning enhances adult neurogenesis in the hippocampal formation. Nat Neurosci, 2(3): 260–265

    Article  CAS  PubMed  Google Scholar 

  • Gould E, McEwen B S, Tanapat P, Galea L A, Fuchs E (1997). Neurogenesis in the dentate gyrus of the adult tree shrew is regulated by psychosocial stress and NMDA receptor activation. J Neurosci, 17 (7): 2492–2498

    CAS  PubMed  Google Scholar 

  • Groves J O, Leslie I, Huang G J, McHugh S B, Taylor A, Mott R, Munafò M, Bannerman D M, Flint J (2013). Ablating adult neurogenesis in the rat has no effect on spatial processing: evidence from a novel pharmacogenetic model. PLoS Genet, 9 (9): e1003718

    Article  CAS  Google Scholar 

  • Gu Y, Arruda-Carvalho M, Wang J, Janoschka S R, Josselyn S A, Frankland P W, Ge S(2012). Optical controlling reveals timedependent roles for adult-born dentate granule cells. Nat Neurosci, 15: 1700–1706

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Guadagno J, Swan P, Shaikh R, Cregan S P (2015). Microglia-derived IL-1beta triggers p53-mediated cell cycle arrest and apoptosis in neural precursor cells. Cell death & disease, 6: e1779

    Article  CAS  Google Scholar 

  • Hanson N D, Owens MJ, Boss-Williams K A, Weiss JM, Nemeroff C B (2011a). Several stressors fail to reduce adult hippocampal neurogenesis. Psychoneuroendocrinology, 36(10): 1520–1529

    Article  PubMed  PubMed Central  Google Scholar 

  • Hanson N D, Owens M J, Nemeroff C B (2011b). Depression, antidepressants, and neurogenesis: a critical reappraisal. Neuropsychopharmacology, 36(13): 2589–2602

    Article  PubMed  PubMed Central  Google Scholar 

  • Harris A P, Holmes M C, de Kloet E R, Chapman K E, Seckl J R (2013). Mineralocorticoid and glucocorticoid receptor balance in control of HPA axis and behaviour. Psychoneuroendocrinology, 38(5): 648–658

    Article  CAS  PubMed  Google Scholar 

  • Heine V M, Maslam S, Joëls M, Lucassen P J (2004a). Increased P27KIP1 protein expression in the dentate gyrus of chronically stressed rats indicates G1 arrest involvement. Neuroscience, 129(3): 593–601

    Article  CAS  PubMed  Google Scholar 

  • Heine V M, Maslam S, Joëls M, Lucassen P J (2004b). Prominent decline of newborn cell proliferation, differentiation, and apoptosis in the aging dentate gyrus, in absence of an age-related hypothalamuspituitary- adrenal axis activation. Neurobiol Aging, 25(3): 361–375

    Article  CAS  PubMed  Google Scholar 

  • Heine V M, Maslam S, Zareno J, Joëls M, Lucassen P J (2004c). Suppressed proliferation and apoptotic changes in the rat dentate gyrus after acute and chronic stress are reversible. Eur J Neurosci, 19 (1): 131–144

    Article  PubMed  Google Scholar 

  • Heine V M, Zareno J, Maslam S, Joëls M, Lucassen P J (2005). Chronic stress in the adult dentate gyrus reduces cell proliferation near the vasculature and VEGF and Flk-1 protein expression. Eur J Neurosci, 21(5): 1304–1314

    Article  PubMed  Google Scholar 

  • Hill A S, Sahay A, Hen R (2015). Increasing adult hippocampal neurogenesis is sufficient to reduce anxiety and depression-like behaviors. Neuropsychopharmacology, 40(10): 2368–2378

    Article  CAS  PubMed  Google Scholar 

  • Hinwood M, Morandini J, Day T A, Walker F R (2012). Evidence that microglia mediate the neurobiological effects of chronic psychological stress on the medial prefrontal cortex. Cereb Cortex, 22(6): 1442–1454

    Article  CAS  PubMed  Google Scholar 

  • Holmes M M, Galea L A, Mistlberger R E, Kempermann G (2004). Adult hippocampal neurogenesis and voluntary running activity: circadian and dose-dependent effects. J Neurosci Res, 76(2): 216–222

    Article  CAS  PubMed  Google Scholar 

  • Hu P, Oomen C, van Dam AM, Wester J, Zhou J N, Joëls M, Lucassen P J (2012). A single-day treatment with mifepristone is sufficient to normalize chronic glucocorticoid induced suppression of hippocampal cell proliferation. PLoS ONE, 7 (9): e46224

    Article  CAS  Google Scholar 

  • Hu P, Wang Y, Liu J, Meng F T, Qi X R, Chen L, van Dam A M, Joëls M, Lucassen P J, Zhou J N (2016). Chronic retinoic acid treatment suppresses adult hippocampal neurogenesis, in close correlation with depressive-like behavior. Hippocampus: doi: 10.1002/hipo.22574

    Google Scholar 

  • Jayatissa M N, Bisgaard C, Tingström A, Papp M, Wiborg O (2006). Hippocampal cytogenesis correlates to escitalopram-mediated recovery in a chronic mild stress rat model of depression. Neuropsychopharmacology, 31(11): 2395–2404

    Article  CAS  PubMed  Google Scholar 

  • Jayatissa M N, Henningsen K, West M J, Wiborg O (2009). Decreased cell proliferation in the dentate gyrus does not associate with development of anhedonic-like symptoms in rats. Brain Res, 1290: 133–141

    Article  CAS  PubMed  Google Scholar 

  • Jessberger S, Gage F H (2014). Adult neurogenesis: bridging the gap between mice and humans. Trends Cell Biol, 24(10): 558–563

    Article  PubMed  Google Scholar 

  • Joca S R, Ferreira F R, Guimarães F S (2007). Modulation of stress consequences by hippocampal monoaminergic, glutamatergic and nitrergic neurotransmitter systems. Stress, 10(3): 227–249

    Article  CAS  PubMed  Google Scholar 

  • Joëls M, Baram T Z (2009). The neuro-symphony of stress. Nat Rev Neurosci, 10(6): 459–466

    PubMed  PubMed Central  Google Scholar 

  • Joëls M, Pu Z, Wiegert O, Oitzl MS, Krugers H J (2006). Learning under stress: how does it work? Trends Cogn Sci, 10(4): 152–158

    Article  PubMed  Google Scholar 

  • Joëls M, Sarabdjitsingh R A, Karst H (2012). Unraveling the time domains of corticosteroid hormone influences on brain activity: rapid, slow, and chronic modes. Pharmacol Rev, 64(4): 901–938

    Article  PubMed  CAS  Google Scholar 

  • Kanatsou S, Fearey B C, Kuil L E, Lucassen P J, Harris A P, Seckl J R, Krugers H, Joels M (2015). Overexpression of Mineralocorticoid Receptors Partially Prevents Chronic Stress-Induced Reductions in Hippocampal Memory and Structural Plasticity. PLoS ONE, 10 (11): e0142012

    Article  CAS  Google Scholar 

  • Kannangara T S, Lucero MJ, Gil-Mohapel J, Drapala R J, Simpson J M, Christie B R, van Praag H (2011). Running reduces stress and enhances cell genesis in aged mice. Neurobiol Aging, 32(12): 2279–2286

    Article  CAS  PubMed  Google Scholar 

  • Karst H, Berger S, Erdmann G, Schütz G, Joëls M(2010). Metaplasticity of amygdalar responses to the stress hormone corticosterone. Proc Natl Acad Sci USA, 107(32): 14449–14454

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kempermann G (2012). New neurons for ‘survival of the fittest’. Nat Rev Neurosci, 13(10): 727–736

    CAS  PubMed  Google Scholar 

  • Kempermann G, Fabel K, Ehninger D, Babu H, Leal-Galicia P, Garthe A, Wolf S A (2010). Why and how physical activity promotes experience-induced brain plasticity. Front Neurosci, 4: 189

    Article  PubMed  PubMed Central  Google Scholar 

  • Kheirbek M A, Klemenhagen K C, Sahay A, Hen R (2012a). Neurogenesis and generalization: a new approach to stratify and treat anxiety disorders. Nat Neurosci, 15(12): 1613–1620

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kheirbek M A, Tannenholz L, Hen R (2012b). NR2B-dependent plasticity of adult-born granule cells is necessary for context discrimination. J Neurosci, 32(25): 8696–8702

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Koolhaas J M, Bartolomucci A, Buwalda B, de Boer S F, Flügge G, Korte SM, Meerlo P, Murison R, Olivier B, Palanza P, Richter-Levin G, Sgoifo A, Steimer T, Stiedl O, van Dijk G, Wöhr M, Fuchs E (2011). Stress revisited: a critical evaluation of the stress concept. Neurosci Biobehav Rev, 35(5): 1291–1301

    Article  CAS  PubMed  Google Scholar 

  • Kreisel T, Frank M G, Licht T, Reshef R, Ben-Menachem-Zidon O, Baratta M V, Maier S F, Yirmiya R (2014). Dynamic microglial alterations underlie stress-induced depressive-like behavior and suppressed neurogenesis. Mol Psychiatry, 19(6): 699–709

    Article  CAS  PubMed  Google Scholar 

  • Kretz O, Reichardt H M, Schütz G, Bock R (1999). Corticotropinreleasing hormone expression is the major target for glucocorticoid feedback-control at the hypothalamic level. Brain Res, 818(2): 488–491

    Article  CAS  PubMed  Google Scholar 

  • Krugers H J, Goltstein P M, van der Linden S, Joëls M (2006). Blockade of glucocorticoid receptors rapidly restores hippocampal CA1 synaptic plasticity after exposure to chronic stress. Eur J Neurosci, 23(11): 3051–3055

    Article  CAS  PubMed  Google Scholar 

  • Kuhn H G, Dickinson-Anson H, Gage F H (1996). Neurogenesis in the dentate gyrus of the adult rat: age-related decrease of neuronal progenitor proliferation. J Neurosci, 16(6): 2027–2033

    CAS  PubMed  Google Scholar 

  • Lagace D C, Donovan MH, De Carolis N A, Farnbauch L A, Malhotra S, Berton O, Nestler E J, Krishnan V, Eisch A J (2010). Adult hippocampal neurogenesis is functionally important for stressinduced social avoidance. Proc Natl Acad Sci USA, 107(9): 4436–4441

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lehmann M L, Brachman R A, Martinowich K, Schloesser R J, Herkenham M (2013). Glucocorticoids orchestrate divergent effects on mood through adult neurogenesis. J Neurosci, 33(7): 2961–2972

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lemaire V, Koehl M, Le Moal M, Abrous D N (2000). Prenatal stress produces learning deficits associated with an inhibition of neurogenesis in the hippocampus. Proc Natl Acad Sci USA, 97(20): 11032–11037

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Levine S (2005). Developmental determinants of sensitivity and resistance to stress. Psychoneuroendocrinology, 30(10): 939–946

    Article  PubMed  Google Scholar 

  • Levone B R, Cryan J F, O’Leary O F (2015). Role of adult hippocampal neurogenesis in stress resilience. Neurobiology of Stress 1. Neurobiol Stress, 1: 147–155

    Article  Google Scholar 

  • Liston C, Cichon J M, Jeanneteau F, Jia Z, Chao M V, Gan W B (2013). Circadian glucocorticoid oscillations promote learning-dependent synapse formation and maintenance. Nat Neurosci, 16(6): 698–705

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Llorens-Martín M, Jurado-Arjona J, Bolós M, Pallas-Bazarra N, Ávila J (2016). Forced swimming sabotages the morphological and synaptic maturation of newborn granule neurons and triggers a unique proinflammatory milieu in the hippocampus. Brain Behav Immun, 53: 242–254

    Article  PubMed  CAS  Google Scholar 

  • Lucassen P J, Fitzsimons C P, Korosi A, Joels M, Belzung C, Abrous D N (2013a). Stressing new neurons into depression? Mol Psychiatry, 18(4): 396–397

    Article  CAS  PubMed  Google Scholar 

  • Lucassen P J, Meerlo P, Naylor A S, van Dam AM, Dayer A G, Fuchs E, Oomen C A, Czéh B (2010). Regulation of adult neurogenesis by stress, sleep disruption, exercise and inflammation: Implications for depression and antidepressant action. Eur Neuropsychopharmacol, 20(1): 1–17

    Article  CAS  PubMed  Google Scholar 

  • Lucassen P J, Naninck E F, van Goudoever J B, Fitzsimons C, Joels M, Korosi A (2013b). Perinatal programming of adult hippocampal structure and function; emerging roles of stress, nutrition and epigenetics. Trends Neurosci, 36(11): 621–631

    Article  CAS  PubMed  Google Scholar 

  • Lucassen P J, Pruessner J, Sousa N, Almeida O F, van Dam A M, Rajkowska G, Swaab D F, Czéh B (2014). Neuropathology of stress. Acta Neuropathol, 127(1): 109–135

    Article  CAS  PubMed  Google Scholar 

  • Lyons D M, Buckmaster P S, Lee A G, Wu C, Mitra R, Duffey L M, Buckmaster C L, Her S, Patel P D, Schatzberg A F (2010). Stress coping stimulates hippocampal neurogenesis in adult monkeys. Proc Natl Acad Sci USA, 107(33): 14823–14827

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mahmoud R, Wainwright S R, Galea L A (2016). Sex hormones and adult hippocampal neurogenesis: Regulation, implications, and potential mechanisms. Front Neuroendocrinol

    Google Scholar 

  • Mak G K, Weiss S (2010). Paternal recognition of adult offspring mediated by newly generated CNS neurons. Nat Neurosci, 13: 753–758

    Article  CAS  PubMed  Google Scholar 

  • Malberg J E, Duman R S (2003). Cell proliferation in adult hippocampus is decreased by inescapable stress: reversal by fluoxetine treatment. Neuropsychopharmacology, 28(9): 1562–1571

    Article  CAS  PubMed  Google Scholar 

  • Marlatt M W, Potter M C, Lucassen P J, van Praag H (2012). Running throughout middle-age improves memory function, hippocampal neurogenesis, and BDNF levels in female C57BL/6J mice. Dev Neurobiol, 72(6): 943–952

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mayer J L, Klumpers L, Maslam S, de Kloet E R, Joëls M, Lucassen P J (2006). Brief treatment with the glucocorticoid receptor antagonist mifepristone normalises the corticosterone-induced reduction of adult hippocampal neurogenesis. J Neuroendocrinol, 18(8): 629–631

    Article  CAS  PubMed  Google Scholar 

  • Meaney M J, Szyf M, Seckl J R (2007). Epigenetic mechanisms of perinatal programming of hypothalamic-pituitary-adrenal function and health. Trends Mol Med, 13(7): 269–277

    Article  CAS  PubMed  Google Scholar 

  • Medina A, Seasholtz A F, Sharma V, Burke S, Bunney W, Myers R M, Schatzberg A, Akil H, Watson S J (2013). Glucocorticoid and mineralocorticoid receptor expression in the human hippocampus in major depressive disorder. J Psychiatr Res, 47(3): 307–314

    Article  PubMed  Google Scholar 

  • Miller J A, Nathanson J, Franjic D, Shim S, Dalley R A, Shapouri S, Smith K A, Sunkin S M, Bernard A, Bennett J L, Lee C K, Hawrylycz M J, Jones A R, Amaral D G, Šestan N, Gage F H, Lein E S (2013). Conserved molecular signatures of neurogenesis in the hippocampal subgranular zone of rodents and primates. Development, 140(22): 4633–4644

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mirescu C, Gould E (2006). Stress and adult neurogenesis. Hippocampus, 16(3): 233–238

    Article  CAS  PubMed  Google Scholar 

  • Mitra R, Sundlass K, Parker K J, Schatzberg A F, Lyons D M (2006). Social stress-related behavior affects hippocampal cell proliferation in mice. Physiol Behav, 89(2): 123–127

    Article  CAS  PubMed  Google Scholar 

  • Montaron M F, Drapeau E, Dupret D, Kitchener P, Aurousseau C, Le Moal M, Piazza P V, Abrous D N (2006). Lifelong corticosterone level determines age-related decline in neurogenesis and memory. Neurobiol Aging, 27(4): 645–654

    Article  CAS  PubMed  Google Scholar 

  • Montaron M F, Koehl M, Lemaire V, Drapeau E, Abrous D N, Le Moal M (2004). Environmentally induced long-term structural changes: cues for functional orientation and vulnerabilities. Neurotox Res, 6(7-8): 571–580

    Article  CAS  PubMed  Google Scholar 

  • Montaron M F, Piazza P V, Aurousseau C, Urani A, Le Moal M, Abrous D N (2003). Implication of corticosteroid receptors in the regulation of hippocampal structural plasticity. Eur J Neurosci, 18(11): 3105–3111

    Article  CAS  PubMed  Google Scholar 

  • Morris G P, Clark I A, Zinn R, Vissel B (2013). Microglia: a new frontier for synaptic plasticity, learning and memory, and neurodegenerative disease research. Neurobiol Learn Mem, 105: 40–53

    Article  CAS  PubMed  Google Scholar 

  • Nacher J, McEwen B S (2006). The role of N-methyl-D-asparate receptors in neurogenesis. Hippocampus, 16(3): 267–270

    Article  CAS  PubMed  Google Scholar 

  • Nishijima T, Llorens-Martín M, Tejeda G S, Inoue K, Yamamura Y, Soya H, Trejo J L, Torres-Alemán I (2013). Cessation of voluntary wheel running increases anxiety-like behavior and impairs adult hippocampal neurogenesis in mice. Behav Brain Res, 245: 34–41

    Article  PubMed  Google Scholar 

  • O’Leary O F, Cryan J F (2014). A ventral view on antidepressant action: roles for adult hippocampal neurogenesis along the dorsoventral axis. Trends Pharmacol Sci, 35(12): 675–687

    Article  PubMed  CAS  Google Scholar 

  • O’Leary O F, O’Connor RM, Cryan J F (2012). Lithium-induced effects on adult hippocampal neurogenesis are topographically segregated along the dorso-ventral axis of stressed mice. Neuropharmacology, 62(1): 247–255

    Article  PubMed  CAS  Google Scholar 

  • Oomen C A, Bekinschtein P, Kent B A, Saksida LM, Bussey T J (2014). Adult hippocampal neurogenesis and its role in cognition. Wiley Interdiscip Rev Cogn Sci, 5(5): 573–587

    Article  PubMed  PubMed Central  Google Scholar 

  • Oomen C A, Girardi C E, Cahyadi R, Verbeek E C, Krugers H, Joëls M, Lucassen P J (2009). Opposite effects of early maternal deprivation on neurogenesis in male versus female rats. PLoS ONE, 4 (1): e3675

    Article  CAS  Google Scholar 

  • Oomen C A, Mayer J L, de Kloet E R, Joëls M, Lucassen P J (2007). Brief treatment with the glucocorticoid receptor antagonist mifepristone normalizes the reduction in neurogenesis after chronic stress. Eur J Neurosci, 26(12): 3395–3401

    Article  PubMed  Google Scholar 

  • Palmer T D, Willhoite A R, Gage F H (2000). Vascular niche for adult hippocampal neurogenesis. J Comp Neurol, 425(4): 479–494

    Article  CAS  PubMed  Google Scholar 

  • Parihar V K, Hattiangady B, Kuruba R, Shuai B, Shetty A K (2011). Predictable chronic mild stress improves mood, hippocampal neurogenesis and memory. Mol Psychiatry, 16(2): 171–183

    Article  CAS  PubMed  Google Scholar 

  • Perera T D, Dwork A J, Keegan K A, Thirumangalakudi L, Lipira C M, Joyce N, Lange C, Higley J D, Rosoklija G, Hen R, Sackeim H A, Coplan J D (2011). Necessity of hippocampal neurogenesis for the therapeutic action of antidepressants in adult nonhuman primates. PLoS ONE, 6 (4): e17600

    Article  CAS  Google Scholar 

  • Pham K, McEwen B S, Ledoux J E, Nader K (2005). Fear learning transiently impairs hippocampal cell proliferation. Neuroscience, 130 (1): 17–24

    Article  CAS  PubMed  Google Scholar 

  • Pham K, Nacher J, Hof P R, McEwen B S (2003). Repeated restraint stress suppresses neurogenesis and induces biphasic PSA-NCAM expression in the adult rat dentate gyrus. Eur J Neurosci, 17(4): 879–886

    Article  PubMed  Google Scholar 

  • Qi X R, Kamphuis W, Wang S, Wang Q, Lucassen P J, Zhou J N, Swaab D F (2013). Aberrant stress hormone receptor balance in the human prefrontal cortex and hypothalamic paraventricular nucleus of depressed patients. Psychoneuroendocrinology, 38(6): 863–870

    Article  CAS  PubMed  Google Scholar 

  • Qian X, Droste S K, Lightman S L, Reul J M, Linthorst A C (2012). Circadian and ultradian rhythms of free glucocorticoid hormone are highly synchronized between the blood, the subcutaneous tissue, and the brain. Endocrinology, 153(9): 4346–4353

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Revest JM, Dupret D, Koehl M, Funk-Reiter C, Grosjean N, Piazza P V, Abrous D N (2009). Adult hippocampal neurogenesis is involved in anxiety-related behaviors. Mol Psychiatry, 14(10): 959–967

    Article  PubMed  Google Scholar 

  • Ridder S, Chourbaji S, Hellweg R, Urani A, Zacher C, Schmid W, Zink M, Hörtnagl H, Flor H, Henn F A, Schütz G, Gass P (2005). Mice with genetically altered glucocorticoid receptor expression show altered sensitivity for stress-induced depressive reactions. J Neurosci, 25(26): 6243–6250

    Article  CAS  PubMed  Google Scholar 

  • Sahay A, Hen R (2007). Adult hippocampal neurogenesis in depression. Nat Neurosci, 10(9): 1110–1115

    Article  CAS  PubMed  Google Scholar 

  • Sahay A, Scobie K N, Hill A S, O’Carroll C M, Kheirbek M A, Burghardt N S, Fenton A A, Dranovsky A, Hen R (2011a). Increasing adult hippocampal neurogenesis is sufficient to improve pattern separation. Nature, 472(7344): 466–470

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sahay A, Wilson D A, Hen R (2011b). Pattern separation: a common function for new neurons in hippocampus and olfactory bulb. Neuron, 70(4): 582–588

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sampedro-Piquero P, Begega A, Arias J L (2014). Increase of glucocorticoid receptor expression after environmental enrichment: relations to spatial memory, exploration and anxiety-related behaviors. Physiol Behav, 129: 118–129

    Article  CAS  PubMed  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(5634): 805–809

    Article  CAS  PubMed  Google Scholar 

  • Sapolsky R M, Uno H, Rebert C S, Finch C E (1990). Hippocampal damage associated with prolonged glucocorticoid exposure in primates. J Neurosci, 10(9): 2897–2902

    CAS  PubMed  Google Scholar 

  • Sarabdjitsingh R A, Conway-Campbell B L, Leggett J D, Waite E J, Meijer O C, de Kloet E R, Lightman S L (2010). Stress responsiveness varies over the ultradian glucocorticoid cycle in a brain-region-specific manner. Endocrinology, 151(11): 5369–5379

    Article  CAS  PubMed  Google Scholar 

  • Sarabdjitsingh R A, Jezequel J, Pasricha N, Mikasova L, Kerkhofs A, Karst H, Groc L, Joëls M (2014). Ultradian corticosterone pulses balance glutamatergic transmission and synaptic plasticity. Proc Natl Acad Sci USA, 111(39): 14265–14270

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sarabdjitsingh R A, Joëls M, de Kloet E R (2012). Glucocorticoid pulsatility and rapid corticosteroid actions in the central stress response. Physiol Behav, 106(1): 73–80

    Article  CAS  PubMed  Google Scholar 

  • Saxe MD, Battaglia F, Wang JW, Malleret G, David D J, Monckton J E, Garcia A D, Sofroniew M V, Kandel E R, Santarelli L, Hen R, Drew M R (2006). Ablation of hippocampal neurogenesis impairs contextual fear conditioning and synaptic plasticity in the dentate gyrus. Proc Natl Acad Sci USA, 103(46): 17501–17506

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schloesser R J, Lehmann M, Martinowich K, Manji H K, Herkenham M (2010). Environmental enrichment requires adult neurogenesis to facilitate the recovery from psychosocial stress. Mol Psychiatry, 15 (12): 1152–1163

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schmidt H D, Duman R S (2007). The role of neurotrophic factors in adult hippocampal neurogenesis, antidepressant treatments and animal models of depressive-like behavior. Behav Pharmacol, 18 (5-6): 391–418

    Article  CAS  PubMed  Google Scholar 

  • Schoenfeld T J, Cameron H A (2015). Adult neurogenesis and mental illness. Neuropsychopharmacology, 40(1): 113–128

    Article  PubMed  Google Scholar 

  • Schoenfeld T J, Gould E (2013). Differential effects of stress and glucocorticoids on adult neurogenesis. Curr Top Behav Neurosci, 15: 139–164

    Article  CAS  PubMed  Google Scholar 

  • Schouten M, Buijink M R, Lucassen P J, Fitzsimons C P (2012). New Neurons in Aging Brains: Molecular Control by Small Non-Coding RNAs. Front Neurosci, 6: 25

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schwabe L, Joëls M, Roozendaal B, Wolf O T, Oitzl M S (2012). Stress effects on memory: an update and integration. Neurosci Biobehav Rev, 36(7): 1740–1749

    Article  PubMed  Google Scholar 

  • Seo D O, Carillo M A, Chih-Hsiung Lim S, Tanaka K F, Drew M R (2015). Adult Hippocampal Neurogenesis Modulates Fear Learning through Associative and Nonassociative Mechanisms. J Neurosci, 35 (32): 11330–11345

    Article  PubMed  PubMed Central  Google Scholar 

  • Shors T J, Miesegaes G, Beylin A, Zhao M, Rydel T, Gould E (2001). Neurogenesis in the adult is involved in the formation of trace memories. Nature, 410(6826): 372–376

    Article  CAS  PubMed  Google Scholar 

  • Shors T J, Townsend D A, Zhao M, Kozorovitskiy Y, Gould E (2002). Neurogenesis may relate to some but not all types of hippocampaldependent learning. Hippocampus, 12(5): 578–584

    Article  PubMed  PubMed Central  Google Scholar 

  • Sierra A, Beccari S, Diaz-Aparicio I, Encinas J M, Comeau S, Tremblay M E (2014). Surveillance, phagocytosis, and inflammation: how never-resting microglia influence adult hippocampal neurogenesis. Neural Plast, 2014: 610343

    PubMed  PubMed Central  Google Scholar 

  • Sierra A, Encinas J M, Deudero J J, Chancey J H, Enikolopov G, Overstreet-Wadiche L S, Tsirka S E, Maletic-Savatic M (2010). Microglia shape adult hippocampal neurogenesis through apoptosiscoupled phagocytosis. Cell Stem Cell, 7(4): 483–495

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Simon M, Czéh B, Fuchs E (2005). Age-dependent susceptibility of adult hippocampal cell proliferation to chronic psychosocial stress. Brain Res, 1049(2): 244–248

    Article  CAS  PubMed  Google Scholar 

  • Snyder J S, Glover L R, Sanzone KM, Kamhi J F, Cameron H A (2009). The effects of exercise and stress on the survival and maturation of adult-generated granule cells. Hippocampus, 19(10): 898–906

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Snyder J S, Grigereit L, Russo A, Seib D R, Brewer M, Pickel J, Cameron H A (2016). A Transgenic Rat for Specifically Inhibiting Adult Neurogenesis. eNeuro, 3 (3): e0064-16.2016 1–13

    Article  Google Scholar 

  • Snyder J S, Hong N S, McDonald R J, Wojtowicz J M (2005). A role for adult neurogenesis in spatial long-term memory. Neuroscience, 130 (4): 843–852

    Article  CAS  PubMed  Google Scholar 

  • Snyder J S, Soumier A, Brewer M, Pickel J, Cameron H A (2011). Adult hippocampal neurogenesis buffers stress responses and depressive behaviour. Nature, 476(7361): 458–461

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sousa N (2016). The dynamics of the stress neuromatrix. Mol Psychiatry, 21(3): 302–312

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sultan S, Li L, Moss J, Petrelli F, Cassé F, Gebara E, Lopatar J, Pfrieger FW, Bezzi P, Bischofberger J, Toni N (2015). Synaptic Integration of Adult-Born Hippocampal Neurons Is Locally Controlled by Astrocytes. Neuron, 88(5): 957–972

    Article  CAS  PubMed  Google Scholar 

  • Surget A, Tanti A, Leonardo E D, Laugeray A, Rainer Q, Touma C, Palme R, Griebel G, Ibarguen-Vargas Y, Hen R, Belzung C (2011). Antidepressants recruit new neurons to improve stress response regulation. Mol Psychiatry, 16(12): 1177–1188

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Swaab D F, Bao A M, Lucassen P J (2005). The stress system in the human brain in depression and neurodegeneration. Ageing Res Rev, 4(2): 141–194

    Article  CAS  PubMed  Google Scholar 

  • Takamura N, Nakagawa S, Masuda T, Boku S, Kato A, Song N, An Y, Kitaichi Y, Inoue T, Koyama T, Kusumi I (2014). The effect of dopamine on adult hippocampal neurogenesis. Prog Neuropsychopharmacol Biol Psychiatry, 50: 116–124

    Article  CAS  PubMed  Google Scholar 

  • Tanapat P, Galea L A, Gould E (1998). Stress inhibits the proliferation of granule cell precursors in the developing dentate gyrus. Int J Dev Neurosci, 16(3-4): 235–239

    Article  CAS  PubMed  Google Scholar 

  • Tanti A, Belzung C (2013). Neurogenesis along the septo-temporal axis of the hippocampus: are depression and the action of antidepressants region-specific? Neuroscience, 252: 234–252

    Article  CAS  PubMed  Google Scholar 

  • Tanti A, Rainer Q, Minier F, Surget A, Belzung C (2012). Differential environmental regulation of neurogenesis along the septo-temporal axis of the hippocampus. Neuropharmacology, 63(3): 374–384

    Article  CAS  PubMed  Google Scholar 

  • Tasker J G (2006). Rapid glucocorticoid actions in the hypothalamus as a mechanism of homeostatic integration. Obesity (Silver Spring), 14 (Suppl 5): 259S–265S

    Article  CAS  PubMed  Google Scholar 

  • Toni N, Laplagne D A, Zhao C, Lombardi G, Ribak C E, Gage F H, Schinder A F (2008). Neurons born in the adult dentate gyrus form functional synapses with target cells. Nat Neurosci, 11(8): 901–907

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tronel S, Belnoue L, Grosjean N, Revest J M, Piazza P V, Koehl M, Abrous D N (2012). Adult-born neurons are necessary for extended contextual discrimination. Hippocampus, 22(2): 292–298

    Article  PubMed  Google Scholar 

  • Ursin H, Eriksen H R (2004). The cognitive activation theory of stress. Psychoneuroendocrinology, 29(5): 567–592

    Article  PubMed  Google Scholar 

  • Vallières L, Campbell I L, Gage F H, Sawchenko P E (2002). Reduced hippocampal neurogenesis in adult transgenic mice with chronic astrocytic production of interleukin-6. J Neurosci, 22(2): 486–492

    PubMed  Google Scholar 

  • van Bokhoven P, Oomen C A, Hoogendijk WJ, Smit A B, Lucassen P J, Spijker S (2011). Reduction in hippocampal neurogenesis after social defeat is long-lasting and responsive to late antidepressant treatment. Eur J Neurosci, 33(10): 1833–1840

    Article  PubMed  Google Scholar 

  • van der Borght K, Meerlo P, Luiten P G, Eggen B J, van der Zee E A (2005). Effects of active shock avoidance learning on hippocampal neurogenesis and plasma levels of corticosterone. Behav Brain Res, 157(1): 23–30

    Article  PubMed  CAS  Google Scholar 

  • van Praag H, Christie B R, Sejnowski T J, Gage F H (1999a). Running enhances neurogenesis, learning, and long-term potentiation in mice. Proc Natl Acad Sci USA, 96(23): 13427–13431

    Article  PubMed  PubMed Central  Google Scholar 

  • van Praag H, Kempermann G, Gage F H (1999b). Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus. Nat Neurosci, 2(3): 266–270

    Article  PubMed  Google Scholar 

  • Veena J, Srikumar B N, Mahati K, Bhagya V, Raju T R, Shankaranarayana Rao B S (2009). Enriched environment restores hippocampal cell proliferation and ameliorates cognitive deficits in chronically stressed rats. J Neurosci Res, 87(4): 831–843

    Article  CAS  PubMed  Google Scholar 

  • Vinkers C H, Joëls M, Milaneschi Y, Kahn R S, Penninx BW, Boks MP (2014). Stress exposure across the life span cumulatively increases depression risk and is moderated by neuroticism. Depress Anxiety, 31(9): 737–745

    Article  PubMed  Google Scholar 

  • Vivar C, Potter M C, Choi J, Lee J Y, Stringer T P, Callaway E M, Gage F H, Suh H, van Praag H (2012). Monosynaptic inputs to new neurons in the dentate gyrus. Nat Commun, 3: 1107

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Vivar C, Potter M C, van Praag H (2013). All about running: synaptic plasticity, growth factors and adult hippocampal neurogenesis. Curr Top Behav Neurosci, 15: 189–210

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vivinetto A L, Suárez M M, Rivarola M A (2013). Neurobiological effects of neonatal maternal separation and post-weaning environmental enrichment. Behav Brain Res, 240: 110–118

    Article  PubMed  Google Scholar 

  • Vollmayr B, Simonis C, Weber S, Gass P, Henn F (2003). Reduced cell proliferation in the dentate gyrus is not correlated with the development of learned helplessness. Biol Psychiatry, 54(10): 1035–1040

    Article  PubMed  Google Scholar 

  • Wang Q, Joels M, Swaab D F, Lucassen P J (2012). Hippocampal GR expression is increased in elderly depressed females. Neuropharmacology, 62(1): 527–533

    Article  CAS  PubMed  Google Scholar 

  • Wang Q, van Heerikhuize J, Aronica E, Kawata M, Seress L, Joels M, Swaab D F, Lucassen P J (2013). Glucocorticoid receptor protein expression in human hippocampus; stability with age. Neurobiol Aging, 34(6): 1662–1673

    Article  CAS  PubMed  Google Scholar 

  • Wei Q, Hebda-Bauer E K, Pletsch A, Luo J, Hoversten M T, Osetek A J, Evans S J, Watson S J, Seasholtz A F, Akil H (2007). Overexpressing the glucocorticoid receptor in forebrain causes an aging-like neuroendocrine phenotype and mild cognitive dysfunction. J Neurosci, 27(33): 8836–8844

    Article  CAS  PubMed  Google Scholar 

  • Westenbroek C, Den Boer J A, Veenhuis M, Ter Horst G J (2004). Chronic stress and social housing differentially affect neurogenesis in male and female rats. Brain Res Bull, 64(4): 303–308

    Article  PubMed  Google Scholar 

  • Wilson C B, Ebenezer P J, McLaughlin L D, Francis J (2014). Predator exposure/psychosocial stress animal model of post-traumatic stress disorder modulates neurotransmitters in the rat hippocampus and prefrontal cortex. PLoS ONE, 9 (2): e89104

    Article  CAS  Google Scholar 

  • Winocur G, Wojtowicz J M, Sekeres M, Snyder J S, Wang S (2006). Inhibition of neurogenesis interferes with hippocampus-dependent memory function. Hippocampus, 16(3): 296–304

    Article  PubMed  Google Scholar 

  • Wojtowicz J M, Askew M L, Winocur G (2008). The effects of running and of inhibiting adult neurogenesis on learning and memory in rats. Eur J Neurosci, 27(6): 1494–1502

    Article  PubMed  Google Scholar 

  • Wong E Y, Herbert J (2004). The corticoid environment: a determining factor for neural progenitors’ survival in the adult hippocampus. Eur J Neurosci, 20(10): 2491–2498

    Article  PubMed  PubMed Central  Google Scholar 

  • Wong E Y, Herbert J (2005). Roles of mineralocorticoid and glucocorticoid receptors in the regulation of progenitor proliferation in the adult hippocampus. Eur J Neurosci, 22(4): 785–792

    Article  PubMed  PubMed Central  Google Scholar 

  • Wong E Y, Herbert J (2006). Raised circulating corticosterone inhibits neuronal differentiation of progenitor cells in the adult hippocampus. Neuroscience, 137(1): 83–92

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wu M V, Shamy J L, Bedi G, Choi CW, Wall M M, Arango V, Boldrini M, Foltin R W, Hen R (2014). Impact of social status and antidepressant treatment on neurogenesis in the baboon hippocampus. Neuropsychopharmacology, 39(8): 1861–1871

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yu S, Patchev A V, Wu Y, Lu J, Holsboer F, Zhang J Z, Sousa N, Almeida O F (2010). Depletion of the neural precursor cell pool by glucocorticoids. Ann Neurol, 67(1): 21–30

    Article  CAS  PubMed  Google Scholar 

  • Yun S, Donovan MH, RossMN, Richardson D R, Reister R, Farnbauch L A, Fischer S J, Riethmacher D, Gershenfeld H K, Lagace D C, Eisch A J (2016). Stress-Induced Anxiety- and Depressive-Like Phenotype Associated with Transient Reduction in Neurogenesis in Adult Nestin-CreERT2/Diphtheria Toxin Fragment A Transgenic Mice. PLoS ONE, 11 (1): e0147256

    Article  CAS  Google Scholar 

  • Zhang C L, Zou Y, He W, Gage F H, Evans RM (2008). A role for adult TLX-positive neural stem cells in learning and behaviour. Nature, 451(7181): 1004–1007

    Article  CAS  PubMed  Google Scholar 

  • Zhao C, Deng W, Gage F H (2008). Mechanisms and functional implications of adult neurogenesis. Cell, 132(4): 645–660

    Article  CAS  PubMed  Google Scholar 

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Lucassen, P.J., Oomen, C.A. Stress, hippocampal neurogenesis and cognition: functional correlations. Front. Biol. 11, 182–192 (2016). https://doi.org/10.1007/s11515-016-1412-4

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