Skip to main content
SpringerLink
Log in

Neurogenesis and Neuroplasticity in Major Depression: Its Therapeutic Implication

  • Chapter
  • First Online:
Major Depressive Disorder

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1305))

Abstract

The neurochemical model of depression, based on monoaminergic theories, does not allow on its own to understand the mechanism of action of antidepressants. This approach does not explain the gap between the immediate biochemical modulations induced by antidepressants and the time required for their clinical action. Several hypotheses have been developed to try to explain more precisely the action of these molecules, each of them involving mechanisms of receptor regulation. At the same time, data on the neuroanatomy of depression converge toward the existence of specific lesions of this pathology. This chapter aims to provide an overview of recent advances in understanding the mechanisms of neural plasticity involved in pathophysiology depression and in its treatment.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 139.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 179.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 249.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  1. Altman J (1963) Differences in the utilization of tritiated leucine by single neurons in normal and exercised rats: an autoradiographic investigation with microdensitometry. Nature 199:777–780

    Article  CAS  PubMed  Google Scholar 

  2. Altman J (1969) Autoradiographic and histological studies of postnatal neurogenesis. IV. Cell proliferation and migration in the anterior forebrain, with special reference to persisting neurogenesis in the olfactory bulb. J Comp Neurol 137:433–457

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  Google Scholar 

  4. Kaplan MS, Hinds JW (1977) Neurogenesis in the adult rat: electron microscopic analysis of light radioautographs. Science 197:1092–1094

    Article  CAS  PubMed  Google Scholar 

  5. Nottebohm F (2002) Neuronal replacement in adult brain. Brain Res Bull 57:737–749

    Article  PubMed  Google Scholar 

  6. Reynolds BA, Weiss S (1992) Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system. Science 255:1707–1710

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  8. Toda T, Gage FH (2018) Review: adult neurogenesis contributes to hippocampal plasticity. Cell Tissue Res 373:693–709

    Article  PubMed  Google Scholar 

  9. Oakes P, Loukas M, Oskouian RJ, Tubbs RS (2017) The neuroanatomy of depression: a review. Clin Anat 30:44–49

    Article  PubMed  Google Scholar 

  10. Liu W, Ge T, Leng Y, Pan Z, Fan J, Yang W, Cui R (2017) The role of neural plasticity in depression: from hippocampus to prefrontal cortex. Neural Plast 2017:6871089. https://doi.org/10.1155/2017/6871089

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Campbell S, Macqueen G (2004) The role of the hippocampus in the pathophysiology of major depression. J Psychiatry Neurosci 29:417–426

    PubMed  PubMed Central  Google Scholar 

  12. Lyons DM, Yang C, Sawyer-Glover AM, Moseley ME, Schatzberg AF (2001) Early life stress and inherited variation in monkey hippocampal volumes. Arch Gen Psychiatry 58:1145–1151

    Article  CAS  PubMed  Google Scholar 

  13. Maller JJ, Broadhouse K, Rush AJ, Gordon E, Koslow S, Grieve SM (2018) Increased hippocampal tail volume predicts depression status and remission to anti-depressant medications in major depression. Mol Psychiatry 23:1737–1744

    Article  CAS  PubMed  Google Scholar 

  14. Zhong M, Wang X, Xiao J, Yi J, Zhu X, Liao J, Wang W, Yao S (2011) Amygdala hyperactivation and prefrontal hypoactivation in subjects with cognitive vulnerability to depression. Biol Psychol 88:233–242

    Article  PubMed  Google Scholar 

  15. Ruhé HG, Koster M, Booij J, van Herk M, Veltman DJ, Schene AH (2014) Occupancy of serotonin transporters in the amygdala by paroxetine in association with attenuation of left amygdala activation by negative faces in major depressive disorder. Psychiatry Res 221:155–161

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  17. Drevets WC (2004) Neuroplasticity in mood disorders. Dialogues Clin Neurosci 6:199–216

    Article  PubMed  PubMed Central  Google Scholar 

  18. Goodwin GM (2016) Neuropsychological and neuroimaging evidence for the involvement of the frontal lobes in depression: 20 years on. J Psychopharmacol 30:1090–1094

    Article  PubMed  Google Scholar 

  19. Nelson BD, Kessel EM, Klein DN, Shankman SA (2018) Depression symptom dimensions and asymmetrical frontal cortical activity while anticipating reward. Psychophysiology 55(1):e12892. https://doi.org/10.1111/psyp.12892

    Article  Google Scholar 

  20. Bond AM, Ming GL, Song H (2015) Adult mammalian neural stem cells and neurogenesis: five decades later. Cell Stem Cell 17:385–395

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Bonaguidi MA, Wheeler MA, Shapiro JS, Stadel RP, Sun GJ, Ming GL, Song H (2011) In vivo clonal analysis reveals self-renewing and multipotent adult neural stem cell characteristics. Cell 145:1142–1155

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Bonaguidi MA, Song J, Ming GL, Song H (2012) A unifying hypothesis on mammalian neural stem cell properties in the adult hippocampus. Curr Opin Neurobiol 22:754–761

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Pardal R, López BJ (2016) Mature neurons modulate neurogenesis through chemical signals acting on neural stem cells. Develop Growth Differ 58:456–462

    Article  Google Scholar 

  24. Aimone JB, Li Y, Lee SW, Clemenson GD, Deng W, Gage FH (2014) Regulation and function of adult neurogenesis: from genes to cognition. Physiol Rev 94:991–1026

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Crowther AJ, Song J (2014) Activity-dependent signaling mechanisms regulating adult hippocampal neural stem cells and their progeny. Neurosci Bull 30:542–556

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Conover JC, Todd KL (2017) Development and aging of a brain neural stem cell niche. Exp Gerontol 94:9–13

    Article  PubMed  Google Scholar 

  27. Namba T, Huttner WB (2017) Neural progenitor cells and their role in the development and evolutionary expansion of the neocortex. Wiley Interdiscip Rev Dev Biol 6(1):e256. https://doi.org/10.1002/wdev.256

    Article  CAS  Google Scholar 

  28. Capilla-Gonzalez V, Herranz-Pérez V, García-Verdugo JM (2015) The aged brain: genesis and fate of residual progenitor cells in the subventricular zone. Front Cell Neurosci 9:365. https://doi.org/10.3389/fncel.2015.00365

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Martoncikova M, Fabianova K, Schreiberova A, Blasko J, Almasiova V, Racekova E (2014) Astrocytic and vascular scaffolding for neuroblast migration in the rostral migratory stream. Curr Neurovasc Res 11:321–329

    Article  CAS  PubMed  Google Scholar 

  30. Carleton A, Petreanu LT, Lansford R, Alvarez-Buylla A, Lledo PM (2003) Becoming a new neuron in the adult olfactory bulb. Nat Neurosci 6:507–518

    Article  CAS  PubMed  Google Scholar 

  31. Morales-Garcia JA, Echeverry-Alzate V, Alonso-Gil S, Sanz-SanCristobal M, Lopez-Moreno JA, Gil C, Martinez A, Santos A, Perez-Castillo A (2017) Phosphodiesterase7 inhibition activates adult neurogenesis in hippocampus and subventricular zone in vitro and in vivo. Stem Cells 35:458–472

    Article  CAS  PubMed  Google Scholar 

  32. Inta D, Cameron HA, Gass P (2015) New neurons in the adult striatum: from rodents to humans. Trends Neurosci 38:517–523

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Li Q-Q, Qiao G-Q, Ma J, Fan H-W, Li Y-B (2015) Cortical neurogenesis in adult rats after ischemic brain injury: most new neurons fail to mature. Neural Regen Res 10:277–285

    Article  PubMed  PubMed Central  Google Scholar 

  34. Lepousez G, Nissant A, Lledo PM (2015) Adult neurogenesis and the future of the rejuvenating brain circuits. Neuron 86:387–401

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  36. Lledo PM, Gheusi G (2006) Adult neurogenesis: from basic research to clinical applications. Bull Acad Natl Med 190:385–400

    PubMed  Google Scholar 

  37. Egeland M, Zunszain PA, Pariante CM (2015) Molecular mechanisms in the regulation of adult neurogenesis during stress. Nat Rev Neurosci 16:189–200

    Article  CAS  PubMed  Google Scholar 

  38. 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  CAS  PubMed  PubMed Central  Google Scholar 

  39. Lepousez G, Nissant A, Lledo PM (2015) Adult neurogenesis and the future of the rejuvenating brain circuits. Neuron 86:387–401

    Article  CAS  PubMed  Google Scholar 

  40. Aasebø IE, Blankvoort S, Tashiro A (2011) Critical maturational period of new neurons in adult dentate gyrus for their involvement in memory formation. Eur J Neurosci 33:1094–1100

    Article  PubMed  Google Scholar 

  41. Drapeau E, Nora AD (2008) Stem cell review series: role of neurogenesis in age-related memory disorders. Aging Cell 7:569–589

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Dennis CV, Suh LS, Rodriguez ML, Kril JJ, Sutherland GT (2016) Human adult neurogenesis across the ages: an immunohistochemical study. Neuropathol Appl Neurobiol 42:621–638

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Gray JD, Kogan JF, Marrocco J, McEwen BS (2017) Genomic and epigenomic mechanisms of glucocorticoids in the brain. Nat Rev Endocrinol 13:661–673

    Article  CAS  PubMed  Google Scholar 

  44. Peeters B, Langouche L, Van den Berghe G (2017) Adrenocortical stress response during the course of critical illness. Compr Physiol 8:283–298

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  46. Vythilingam M, Vermetten E, Anderson GM, Luckenbaugh D, Anderson ER, Snow J, Staib LH, Charney DS, Bremner JD (2004) Hippocampal volume, memory, and cortisol status in major depressive disorder: effects of treatment. Biol Psychiatry 56:101–112

    Article  CAS  PubMed  Google Scholar 

  47. Koutmani Y, Politis PK, Elkouris M, Agrogiannis G, Kemerli M, Patsouris E, Remboutsika E, Karalis KP (2013) Corticotropin-releasing hormone exerts direct effects on neuronal progenitor cells: implications for neuroprotection. Mol Psychiatry 18:300–307

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Bothwell M (2014) NGF, BDNF, NT3, and NT4. Handb Exp Pharmacol 220:3–15

    Article  CAS  PubMed  Google Scholar 

  49. Hing B, Sathyaputri L, Potash JB (2018) A comprehensive review of genetic and epigenetic mechanisms that regulate BDNF expression and function with relevance to major depressive disorder. Am J Med Genet B Neuropsychiatr Genet 177:143–167

    Article  CAS  PubMed  Google Scholar 

  50. Sandhya VK, Raju R, Verma R, Advani J, Sharma R, Radhakrishnan A, Nanjappa V, Narayana J, Somani BL, Mukherjee KK, Pandey A, Christopher R, Prasad TS (2013) A network map of BDNF/TRKB and BDNF/p75NTR signaling system. J Cell Commun Signal 7:301–307

    Article  PubMed  PubMed Central  Google Scholar 

  51. Kojima M, Mizui T (2017) BDNF propeptide: a novel modulator of synaptic plasticity. Vitam Horm 104:19–28

    Article  CAS  PubMed  Google Scholar 

  52. Martin JL, Finsterwald C (2011) Cooperation between BDNF and glutamate in the regulation of synaptic transmission and neuronal development. Commun Integr Biol 4:14–16

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Colino-Oliveira M, Rombo DM, Dias RB, Ribeiro JA, Sebastião AM (2016) BDNF-induced presynaptic facilitation of GABAergic transmission in the hippocampus of young adults is dependent of TrkB and adenosine A2A receptors. Purinergic Signal 12:283–294

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Szapacs ME, Mathews TA, Tessarollo L, Ernest Lyons W, Mamounas LA, Andrews AM (2004) Exploring the relationship between serotonin and brain-derived neurotrophic factor: analysis of BDNF protein and extraneuronal 5-HT in mice with reduced serotonin transporter or BDNF expression. J Neurosci Methods 140:81–92

    Article  CAS  PubMed  Google Scholar 

  55. Narita M, Aoki K, Takagi M, Yajima Y, Suzuki T (2003) Implication of brain-derived neurotrophic factor in the release of dopamine and dopamine-related behaviors induced by methamphetamine. Neuroscience 119:767–775

    Article  CAS  PubMed  Google Scholar 

  56. D’Sa C, Duman RS (2002) Antidepressants and neuroplasticity. Bipolar Disord 4:183–194

    Article  PubMed  Google Scholar 

  57. Khakpai F, Zarrindast MR, Nasehi M, Haeri-Rohani A, Eidi A (2013) The role of glutamatergic pathway between septum and hippocampus in the memory formation. EXCLI J 12:41–51. eCollection 2013

    PubMed  PubMed Central  Google Scholar 

  58. Joca SR, Ferreira FR, Guimarães FS (2007) Modulation of stress consequences by hippocampal monoaminergic, glutamatergic and nitrergic neurotransmitter systems. Stress 10:227–249

    Article  CAS  PubMed  Google Scholar 

  59. Manji HK, Quiroz JA, Sporn J, Payne JL, Denicoff KA, Gray N, Zarate CA Jr, Charney DS (2003) Enhancing neuronal plasticity and cellular resilience to develop novel, improved therapeutics for difficult-to-treat depression. Biol Psychiatry 53:707–742

    Article  CAS  PubMed  Google Scholar 

  60. McEwen BS (1997) Possible mechanisms for atrophy of the human hippocampus. Mol Psychiatry 2:255–262

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  62. Villa RF, Ferrari F, Moretti A (2018) Post-stroke depression: mechanisms and pharmacological treatment. Pharmacol Ther 184:131–144

    Article  CAS  PubMed  Google Scholar 

  63. 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  CAS  PubMed  Google Scholar 

  64. Cantone M, Bramanti A, Lanza G, Pennisi M, Bramanti P, Pennisi G, Bella R (2017) Cortical plasticity in depression. ASN Neuro 9(3):1759091417711512

    Article  PubMed  PubMed Central  Google Scholar 

  65. Kraus C, Castrén E, Kasper S, Lanzenberger R (2017) Serotonin and neuroplasticity—links between molecular, functional and structural pathophysiology in depression. Neurosci Biobehav Rev 77:317–326

    Article  CAS  PubMed  Google Scholar 

  66. Liguz-Lecznar M, Lehner M, Kaliszewska A, Zakrzewska R, Sobolewska A, Kossut M (2015) Altered glutamate/GABA equilibrium in aged mice cortex influences cortical plasticity. Brain Struct Funct 220:1681–1693

    Article  CAS  PubMed  Google Scholar 

  67. Greger IH, Watson JF, Cull-Candy SG (2017) Structural and functional architecture of AMPA-type glutamate receptors and their auxiliary proteins. Neuron 94:713–730

    Article  CAS  PubMed  Google Scholar 

  68. Réus GZ, Abelaira HM, Tuon T, Titus SE, Ignácio ZM, Rodrigues AL, Quevedo J (2016) Glutamatergic NMDA receptor as therapeutic target for depression. Adv Protein Chem Struct Biol 103:169–202

    Article  PubMed  CAS  Google Scholar 

  69. Bourin M (2019) Why ketamine is a new treatment of resistant depression? SOJ Pharm Sci 6(2):1–3. https://doi.org/10.15226/2374-6866/6/2/00198

    Article  Google Scholar 

  70. Levy MJF, Boulle F, Steinbusch HW, van den Hove DLA, Kenis G, Lanfumey L (2018) Neurotrophic factors and neuroplasticity pathways in the pathophysiology and treatment of depression. Psychopharmacology 235:2195–2220

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    PubMed  PubMed Central  Google Scholar 

  72. Sahay A, Drew MR, Hen R (2007) Dentate gyrus neurogenesis and depression. Prog Brain Res 163:697–722

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  74. Castrén E, Kojima M (2017) Brain-derived neurotrophic factor in mood disorders and antidepressant treatments. Neurobiol Dis 97(Pt B):119–126

    Article  PubMed  CAS  Google Scholar 

  75. Ostadhadi S, Ahangari M, Nikoui V, Norouzi-Javidan A, Zolfaghari S, Jazaeri F, Chamanara M, Akbarian R, Dehpour AR (2016) Pharmacological evidence for the involvement of the NMDA receptor and nitric oxide pathway in the antidepressant-like effect of lamotrigine in the mouse forced swimming test. Biomed Pharmacother 82:713–721

    Article  CAS  PubMed  Google Scholar 

  76. Bourin M, Hascoet M, Masse F (2005) Evidence of the activity of lamotrigine on 5-HT1A receptors in the mouse forced swimming test. J Psychiatry Neurosci 30:275–282

    PubMed  PubMed Central  Google Scholar 

  77. Okada M, Fukuyama K, Kawano Y, Shiroyama T, Ueda Y (2019) Memantine protects thalamocortical hyper-glutamatergic transmission induced by NMDA receptor antagonism via activation of system xc. Pharmacol Res Perspect 7(1):e00457. https://doi.org/10.1002/prp2.457

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Khan AJ, LaCava S, Mehta M, Schiff D, Thandoni A, Jhawar S, Danish S, Haffty BG, Chen S (2019) The glutamate release inhibitor riluzole increases DNA damage and enhances cytotoxicity in human glioma cells, in vitro and in vivo. Oncotarget 10:2824–2834

    Article  PubMed  PubMed Central  Google Scholar 

  79. Dutta A, McKie S, Deakin JFW (2015) Ketamine and other potential glutamate antidepressants. Psychiatry Res 225:1–13

    Article  CAS  PubMed  Google Scholar 

  80. Kanzari A, Bourcier-Lucas C, Freyssin A, Abrous DN, Haddjeri N, Lucas G (2018) Inducing a long-term potentiation in the dentate gyrus is sufficient to produce rapid antidepressant-like effects. Mol Psychiatry 23:587–596

    Article  CAS  PubMed  Google Scholar 

  81. Eliwa H, Belzung C, Surget A (2017) Adult hippocampal neurogenesis: is it the alpha and omega of antidepressant action? Biochem Pharmacol 141:86–99

    Article  CAS  PubMed  Google Scholar 

  82. Strawbridge WJ, Deleger S, Roberts RE, Kaplan GA (2002) Physical activity reduces the risk of subsequent depression for older adults. Am J Epidemiol 156:328–334

    Article  PubMed  Google Scholar 

  83. Van Praag H, Kempermann G, Gage FH (1999) Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus. Nat Neurosci 2:266–270

    Article  PubMed  Google Scholar 

  84. Bourin M (2018) Post-stroke depression and changes in behavior and personality. Arch Depress Anxiety 4(1):031–033

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Neurobiology of Mood Disorders, University of Nantes, Nantes, France

    Michel Bourin

Authors
  1. Michel Bourin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Michel Bourin .

Editor information

Editors and Affiliations

  1. Department of Psychiatry, Korea University Ansan Hospital, College of Medicine, Ansan, Korea (Republic of)

    Yong-Ku Kim

Rights and permissions

Reprints and permissions

Copyright information

© 2021 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Bourin, M. (2021). Neurogenesis and Neuroplasticity in Major Depression: Its Therapeutic Implication. In: Kim, YK. (eds) Major Depressive Disorder. Advances in Experimental Medicine and Biology, vol 1305. Springer, Singapore. https://doi.org/10.1007/978-981-33-6044-0_10

Download citation

Publish with us

Policies and ethics

Search

Navigation