Skip to main content

Advertisement

SpringerLink
Log in

Neurogenesis in the aged and neurodegenerative brain

  • Apoptosis in the aging brain
  • Published:
Apoptosis Aims and scope Submit manuscript

Abstract

It has been well established that adult neurogenesis occurs throughout life in the subventricular (SVZ) and subgranular (SGZ) zones. However, the exact role of this type of brain plasticity is not yet clear. Many studies have shown that neurogenesis is involved in learning and memory. This has led to a hypothesis which suggests that impairment in memory during aging and neurodegenerative diseases such as Alzheimer’s disease (AD) may involve abnormal neurogenesis. Indeed, during aging, there is an age-related decline in adult neurogenesis. This decline is mostly related to decreased proliferation, associated to decreased stimulation to proliferate in an aging brain. In AD, there is also evidence for decreased neurogenesis, that accompanies the neuronal loss characteristic of the disease. Interestingly in AD, there is increased proliferation, that may be caused by increasing amounts of soluble amyloid ß42-protein (Aβ42). However, most of these new neurons die, and fibrillar Aβ42 seems to be involved in generating an inappropriate environment for these neurons to mature. These findings open prospects for new strategies that can increase neurogenesis in normal or pathological processes in the aging brain, and by that decrease memory deficits.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

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

    Article  CAS  PubMed  Google Scholar 

  2. Emsley J, Mitchell B, Kempermann G, Macklis J (2005) Adult neurogenesis and repair of the adult CNS with neural progenitors, precursors, and stem cells. Prog Neurobiol 75:321–341

    Article  CAS  PubMed  Google Scholar 

  3. Martin S, Grimwood P, Morris R (2000) Synaptic plasticity and memory: an evaluation of the hypothesis. Annu Rev Neurosci 23:649–711

    Article  CAS  PubMed  Google Scholar 

  4. Luine V, Villegas M, Martinez C, McEwen B (1994) Repeated stress causes reversible impairments of spatial memory performance. Brain Res 639:167–170

    Article  CAS  PubMed  Google Scholar 

  5. Diamond D, Park C, Heman K, Rose G (1999) Exposing rats to a predator impairs spatial working memory in the radial arm water maze. Hippocampus 9:542–552

    Article  CAS  PubMed  Google Scholar 

  6. Tanapat P, Hastings N, Reeves A, 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

    CAS  PubMed  Google Scholar 

  7. Tanapat P, Hastings N, Rydel T, Galea L, Gould E (2001) Exposure to fox odor inhibits cell proliferation in the hippocampus of adult rats via an adrenal hormone-dependent mechanism. J Comp Neurol 437:496–504

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  12. Wood G, Beylin A, Shors T (2001) The contribution of adrenal and reproductive hormones to the opposing effects of stress on trace conditioning in males versus females. Behav Neurosci 115:175–187

    Article  CAS  PubMed  Google Scholar 

  13. Holmes M, Wide J, Galea L (2002) Low levels of estradiol facilitate, whereas high levels of estradiol impair, working memory performance on the radial arm maze. Behav Neurosci 116:928–934

    Article  CAS  PubMed  Google Scholar 

  14. Bartolomucci A, de Biurrun G, Czéh B, van Kampen M, Fuchs E (2002) Selective enhancement of spatial learning under chronic psychosocial stress. Eur J Neurosci 15:1863–1866

    Article  PubMed  Google Scholar 

  15. Leuner B, Mendolia-Loffredo S, Kozorovitskiy Y, Samburg D, Gould E, Shors T (2004) Learning enhances the survival of new neurons beyond the time when the hippocampus is required for memory. J Neurosci 24:7477–7481

    Article  CAS  PubMed  Google Scholar 

  16. Döbrössy M, Drapeau E, Aurousseau C, Le Moal M, Piazza P, Abrous D (2003) Differential effects of learning on neurogenesis: learning increases or decreases the number of newly born cells depending on their birth date. Mol Psychiatry 8:974–982

    Article  PubMed  Google Scholar 

  17. Hairston I, Little M, Scanlon M et al (2005) Sleep restriction suppresses neurogenesis induced by hippocampus-dependent learning. J Neurophysiol 94:4224–4233

    Article  PubMed  Google Scholar 

  18. Ambrogini P, Orsini L, Mancini C, Ferri P, Ciaroni S, Cuppini R (2004) Learning may reduce neurogenesis in adult rat dentate gyrus. Neurosci Lett 359:13–16

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  21. Olariu A, Cleaver K, Shore L, Brewer M, Cameron H (2005) A natural form of learning can increase and decrease the survival of new neurons in the dentate gyrus. Hippocampus 15:750–762

    Article  PubMed  Google Scholar 

  22. Van der Borght K, Wallinga A, Luiten P, Eggen B, Van der Zee E (2005) Morris water maze learning in two rat strains increases the expression of the polysialylated form of the neural cell adhesion molecule in the dentate gyrus but has no effect on hippocampal neurogenesis. Behav Neurosci 119:926–932

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  25. Shors T, Townsend D, Zhao M, Kozorovitskiy Y, Gould E (2002) Neurogenesis may relate to some but not all types of hippocampal-dependent learning. Hippocampus 12:578–584

    Article  PubMed  Google Scholar 

  26. Hattiangady B, Shetty A (2008) Aging does not alter the number or phenotype of putative stem/progenitor cells in the neurogenic region of the hippocampus. Neurobiol Aging 29:129–147

    Article  CAS  PubMed  Google Scholar 

  27. Aizawa K, Ageyama N, Terao K, Hisatsune T (2009) Primate-specific alterations in neural stem/progenitor cells in the aged hippocampus. Neurobiol Aging (in press)

  28. Rao M, Hattiangady B, Abdel-Rahman A, Stanley D, Shetty A (2005) Newly born cells in the ageing dentate gyrus display normal migration, survival and neuronal fate choice but endure retarded early maturation. Eur J Neurosci 21:464–476

    Article  PubMed  Google Scholar 

  29. Bondolfi L, Ermini F, Long J, Ingram D, Jucker M (2004) Impact of age and caloric restriction on neurogenesis in the dentate gyrus of C57BL/6 mice. Neurobiol Aging 25:333–340

    Article  CAS  PubMed  Google Scholar 

  30. Enwere E, Shingo T, Gregg C, Fujikawa H, Ohta S, Weiss S (2004) Aging results in reduced epidermal growth factor receptor signaling, diminished olfactory neurogenesis, and deficits in fine olfactory discrimination. J Neurosci 24:8354–8365

    Article  CAS  PubMed  Google Scholar 

  31. Cuppini R, Bucherelli C, Ambrogini P et al (2006) Age-related naturally occurring depression of hippocampal neurogenesis does not affect trace fear conditioning. Hippocampus 16:141–148

    Article  PubMed  Google Scholar 

  32. Molofsky A, Slutsky S, Joseph N et al (2006) Increasing p16INK4a expression decreases forebrain progenitors and neurogenesis during ageing. Nature 443:448–452

    Article  CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  34. Lichtenwalner R, Forbes M, Bennett S, Lynch C, Sonntag W, Riddle D (2001) Intracerebroventricular infusion of insulin-like growth factor-I ameliorates the age-related decline in hippocampal neurogenesis. Neuroscience 107:603–613

    Article  CAS  PubMed  Google Scholar 

  35. McDonald H, Wojtowicz J (2005) Dynamics of neurogenesis in the dentate gyrus of adult rats. Neurosci Lett 385:70–75

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  38. Driscoll I, Howard S, Stone J et al (2006) The aging hippocampus: a multi-level analysis in the rat. Neuroscience 139:1173–1185

    Article  CAS  PubMed  Google Scholar 

  39. Kempermann G, Brandon E, Gage F (1998) Environmental stimulation of 129/SvJ mice causes increased cell proliferation and neurogenesis in the adult dentate gyrus. Curr Biol 8:939–942

    Article  CAS  PubMed  Google Scholar 

  40. Jin K, Sun Y, Xie L et al (2003) Neurogenesis and aging: FGF-2 and HB-EGF restore neurogenesis in hippocampus and subventricular zone of aged mice. Aging Cell 2:175–183

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  42. Sapolsky R (1992) Do glucocorticoid concentrations rise with age in the rat? Neurobiol Aging 13:171–174

    Article  CAS  PubMed  Google Scholar 

  43. Cameron H, McKay R (1999) Restoring production of hippocampal neurons in old age. Nat Neurosci 2:894–897

    Article  CAS  PubMed  Google Scholar 

  44. Mohs R, Schmeidler J, Aryan M (2000) Longitudinal studies of cognitive, functional and behavioural change in patients with Alzheimer’s disease. Stat Med 19:1401–1409

    Article  CAS  PubMed  Google Scholar 

  45. Haass C, Selkoe D (2007) Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer’s amyloid beta-peptide. Nat Rev Mol Cell Biol 8:101–112

    Article  CAS  PubMed  Google Scholar 

  46. Ziabreva I, Perry E, Perry R et al (2006) Altered neurogenesis in Alzheimer’s disease. J Psychosom Res 61:311–316

    Article  PubMed  Google Scholar 

  47. Lovell M, Geiger H, Van Zant G, Lynn B, Markesbery W (2006) Isolation of neural precursor cells from Alzheimer’s disease and aged control postmortem brain. Neurobiol Aging 27:909–917

    Article  PubMed  Google Scholar 

  48. Nagy Z, Esiri M, Smith A (1997) Expression of cell division markers in the hippocampus in Alzheimer’s disease and other neurodegenerative conditions. Acta Neuropathol 93:294–300

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  50. Jin K, Peel A, Mao X et al (2004) Increased hippocampal neurogenesis in Alzheimer’s disease. Proc Natl Acad Sci USA 101:343–347

    Article  CAS  PubMed  Google Scholar 

  51. Li B, Yamamori H, Tatebayashi Y et al (2008) Failure of neuronal maturation in Alzheimer disease dentate gyrus. J Neuropathol Exp Neurol 67:78–84

    Article  CAS  PubMed  Google Scholar 

  52. Jin K, Galvan V, Xie L et al (2004) Enhanced neurogenesis in Alzheimer’s disease transgenic (PDGF-APPSw, Ind) mice. Proc Natl Acad Sci USA 101:13363–13367

    Article  CAS  PubMed  Google Scholar 

  53. López-Toledano M, Shelanski M (2007) Increased neurogenesis in young transgenic mice overexpressing human APP (Sw, Ind). J Alzheimers Dis 12:229–240

    PubMed  Google Scholar 

  54. Donovan M, Yazdani U, Norris R, Games D, German D, Eisch A (2006) Decreased adult hippocampal neurogenesis in the PDAPP mouse model of Alzheimer’s disease. J Comp Neurol 495:70–83

    Article  PubMed  Google Scholar 

  55. Haughey N, Nath A, Chan S, Borchard A, Rao M, Mattson M (2002) Disruption of neurogenesis by amyloid beta-peptide, and perturbed neural progenitor cell homeostasis, in models of Alzheimer’s disease. J Neurochem 83:1509–1524

    Article  CAS  PubMed  Google Scholar 

  56. Wen P, Hof P, Chen X et al (2004) The presenilin-1 familial Alzheimer disease mutant P117L impairs neurogenesis in the hippocampus of adult mice. Exp Neurol 188:224–237

    Article  CAS  PubMed  Google Scholar 

  57. Wang R, Dineley K, Sweatt J, Zheng H (2004) Presenilin 1 familial Alzheimer’s disease mutation leads to defective associative learning and impaired adult neurogenesis. Neuroscience 126:305–312

    Article  CAS  PubMed  Google Scholar 

  58. Verret L, Jankowsky J, Xu G, Borchelt D, Rampon C (2007) Alzheimer’s-type amyloidosis in transgenic mice impairs survival of newborn neurons derived from adult hippocampal neurogenesis. J Neurosci 27:6771–6780

    Article  CAS  PubMed  Google Scholar 

  59. Zhang C, McNeil E, Dressler L, Siman R (2007) Long-lasting impairment in hippocampal neurogenesis associated with amyloid deposition in a knock-in mouse model of familial Alzheimer’s disease. Exp Neurol 204:77–87

    Article  CAS  PubMed  Google Scholar 

  60. Yu Y, He J, Zhang Y et al (2009) Increased hippocampal neurogenesis in the progressive stage of Alzheimer’s disease phenotype in an APP/PS1 double transgenic mouse model. Hippocampus 19:1247–1253

    Article  PubMed  Google Scholar 

  61. Rodríguez J, Jones V, Tabuchi M et al (2008) Impaired adult neurogenesis in the dentate gyrus of a triple transgenic mouse model of Alzheimer’s disease. PLoS One 3:e2935

    Article  PubMed  Google Scholar 

  62. Chen Q, Nakajima A, Choi S, Xiong X, Sisodia S, Tang Y (2008) Adult neurogenesis is functionally associated with AD-like neurodegeneration. Neurobiol Dis 29:316–326

    Article  CAS  PubMed  Google Scholar 

  63. López-Toledano M, Shelanski M (2004) Neurogenic effect of beta-amyloid peptide in the development of neural stem cells. J Neurosci 24:5439–5444

    Article  PubMed  Google Scholar 

  64. Heo C, Chang K, Choi H et al (2007) Effects of the monomeric, oligomeric, and fibrillar Abeta42 peptides on the proliferation and differentiation of adult neural stem cells from subventricular zone. J Neurochem 102:493–500

    Article  CAS  PubMed  Google Scholar 

  65. Chen Y, Dong C (2009) Abeta40 promotes neuronal cell fate in neural progenitor cells. Cell Death Differ 16:386–394

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The work presented in this manuscript was supported, in part, by the Norma and Alan Aufzein Chair for Parkinson’s Disease Research and the Devora Eleonora Kirshman Fund for Research of Parkinson’s Disease, Tel-Aviv University.

Author information

Authors and Affiliations

  1. The Neuroscience Laboratory, Felsenstein Medical Research Center, Sackler School of Medicine, Tel-Aviv University, Ramat Aviv, Israel

    Adi Shruster, Eldad Melamed & Daniel Offen

Authors
  1. Adi Shruster
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Eldad Melamed
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Daniel Offen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Daniel Offen.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Shruster, A., Melamed, E. & Offen, D. Neurogenesis in the aged and neurodegenerative brain. Apoptosis 15, 1415–1421 (2010). https://doi.org/10.1007/s10495-010-0491-y

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10495-010-0491-y

Keywords

Search

Navigation