Home LiteratureArticle Details
PMID: 14614143 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Spatial memory performances of aged rats in the water maze predict levels of hippocampal neurogenesis.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 100 ·No. 24 ·2003-11-25 ·Pages 14385-90

Drapeau E, Mayo W, Aurousseau C, Le Moal M, Piazza PV, Abrous DN

Abstract

Neurogenesis occurs within the adult dentate gyrus of the hippocampal formation and it has been proposed that the newly born neurons, recruited into the preexistent neuronal circuits, might be involved in hippocampal-dependent learning processes. Age-dependent spatial memory impairments have been related to an alteration in hippocampal plasticity. The aim of the current study was to examine whether cognitive functions in aged rats are quantitatively correlated with hippocampal neurogenesis. To this end, we took advantage of the existence of spontaneous individual differences observed in aged subjects in a hippocampal-dependent task, the water maze. We expected that the spatial memory capabilities of aged rats would be related to the levels of hippocampal neurogenesis. Old rats were trained in the water maze, and, 3 weeks after training, rats were injected with 5-bromo-2'-deoxyuridine (BrdUrd, 50 or 150 mg/kg) to label dividing cells. Cell proliferation was examined one day after the last BrdUrd injection, whereas cell survival and differentiation were determined 3 weeks later. It is shown that a quantitative relationship exists between learning and the number of newly generated neurons. Animals with preserved spatial memory, i.e., the aged-unimpaired rats, exhibited a higher level of cell proliferation and a higher number of new neurons in comparison with rats with spatial memory impairments, i.e., the aged-impaired rats. In conclusion, the extent of memory dysfunction in aged rats is quantitatively related to the hippocampal neurogenesis. These data reinforce the assumption that neurogenesis is involved in memory processes and aged-related cognitive alterations.

MeSH Terms
Aging/psychology Animals Bromodeoxyuridine/metabolism Cell Division Cell Survival Hippocampus/cytology,growth & development,physiology Male Maze Learning/physiology Memory/physiology Rats Rats, Sprague-Dawley Spatial Behavior/physiology
Chemicals
Bromodeoxyuridine
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Drapeau Elodie
Institut National de la Santá et de la Recherche Médicale Unité 588, Domaine de Carreire, Rue Camille Saint Saëns, University of Bordeaux II, 33077 Bordeaux Cedex, France.
Mayo Willy
Aurousseau Catherine
Le Moal Michel
Piazza Pier-Vincenzo
Abrous Djoher Nora
References (65)
65 references, click to expand
  1. Prenatal stress produces learning deficits associated with an inhibition of neurogenesis in the hippocampus.
    Proc Natl Acad Sci U S A. 2000 Sep 26;97(20):11032-7 PMID: 11005874
  2. Are new neurons formed in the brains of adult mammals?
    Science. 1962 Mar 30;135(3509):1127-8 PMID: 13860748
  3. Antibodies against the Ki-67 protein: assessment of the growth fraction and tools for cell cycle analysis.
    Methods Cell Biol. 2001;63:399-418 PMID: 11060851
  4. Neurogenesis in the adult brain: death of a dogma.
    Nat Rev Neurosci. 2000 Oct;1(1):67-73 PMID: 11252770
  5. Neurogenesis in the adult is involved in the formation of trace memories.
    Nature. 2001 Mar 15;410(6826):372-6 PMID: 11268214
  6. Gender and strain influence on neurogenesis in dentate gyrus of young rats.
    J Cereb Blood Flow Metab. 2001 Mar;21(3):211-7 PMID: 11295875
  7. Adult neurogenesis produces a large pool of new granule cells in the dentate gyrus.
    J Comp Neurol. 2001 Jul 9;435(4):406-17 PMID: 11406822
  8. Intracerebroventricular infusion of insulin-like growth factor-I ameliorates the age-related decline in hippocampal neurogenesis.
    Neuroscience. 2001;107(4):603-13 PMID: 11720784
  9. Serotonin mediates oestrogen stimulation of cell proliferation in the adult dentate gyrus.
    Eur J Neurosci. 2001 Nov;14(9):1417-24 PMID: 11722603
  10. Hippocampal plasticity in Alzheimer's disease.
    Rev Neurosci. 2001;12(4):311-25 PMID: 11783717
  11. Neurogenesis in adult primate neocortex: an evaluation of the evidence.
    Nat Rev Neurosci. 2002 Jan;3(1):65-71 PMID: 11823806
  12. Adult neurogenesis in mammals: an identity crisis.
    J Neurosci. 2002 Feb 1;22(3):614-8 PMID: 11826088
  13. Why are some neurons replaced in adult brain?
    J Neurosci. 2002 Feb 1;22(3):624-8 PMID: 11826090
  14. Why new neurons? Possible functions for adult hippocampal neurogenesis.
    J Neurosci. 2002 Feb 1;22(3):635-8 PMID: 11826092
  15. Functional neurogenesis in the adult hippocampus.
    Nature. 2002 Feb 28;415(6875):1030-4 PMID: 11875571
  16. Nicotine self-administration impairs hippocampal plasticity.
    J Neurosci. 2002 May 1;22(9):3656-62 PMID: 11978841
  17. Neuronal replacement in adult brain.
    Brain Res Bull. 2002 Apr;57(6):737-49 PMID: 12031270
  18. Neurogenesis may relate to some but not all types of hippocampal-dependent learning.
    Hippocampus. 2002;12(5):578-84 PMID: 12440573
  19. NMDA receptor antagonist treatment increases the production of new neurons in the aged rat hippocampus.
    Neurobiol Aging. 2003 Mar-Apr;24(2):273-84 PMID: 12498961
  20. Is it only neurogenesis?
    Rev Neurosci. 2002;13(4):375-82 PMID: 12542263
  21. Hippocampal cell genesis does not correlate with spatial learning ability in aged rats.
    J Comp Neurol. 2003 Apr 28;459(2):201-7 PMID: 12640670
  22. Hippocampal aging and adrenocorticoids: quantitative correlations.
    Science. 1978 Dec 8;202(4372):1098-102 PMID: 715460
  23. Memory deficits associated with senescence: a neurophysiological and behavioral study in the rat.
    J Comp Physiol Psychol. 1979 Feb;93(1):74-104 PMID: 221551
  24. Regional changes in brain glucose metabolism reflect cognitive impairments in aged rats.
    J Neurosci. 1984 Nov;4(11):2856-65 PMID: 6502208
  25. Loss of perforated synapses in the dentate gyrus: morphological substrate of memory deficit in aged rats.
    Proc Natl Acad Sci U S A. 1986 May;83(9):3027-31 PMID: 3458260
  26. Aged rats need a preserved complement of perforated axospinous synapses per hippocampal neuron to maintain good spatial memory.
    Brain Res. 1986 Nov 29;398(2):266-75 PMID: 3801904
  27. Aging and the physiology of spatial memory.
    Neurobiol Aging. 1988 Sep-Dec;9(5-6):563-8 PMID: 3062467
  28. Age-dependent alterations in hippocampal synaptic plasticity: relation to memory disorders.
    Neurobiol Aging. 1988 Sep-Dec;9(5-6):581-90 PMID: 3062469
  29. Experimental approaches to age-related cognitive impairments.
    Neurobiol Aging. 1988 Sep-Dec;9(5-6):645-55 PMID: 3062473
  30. From bird song to neurogenesis.
    Sci Am. 1989 Feb;260(2):74-9 PMID: 2643827
  31. Evidence that granule cells generated in the dentate gyrus of adult rats extend axonal projections.
    Exp Brain Res. 1988;72(2):399-406 PMID: 2465172
  32. Individual differences in aging: behavioral and neurobiological correlates.
    Neurobiol Aging. 1989 Jan-Feb;10(1):31-43 PMID: 2569170
  33. Age-related structural changes in the rat hippocampus: correlation with working memory deficiency.
    Brain Res. 1990 Mar 26;512(1):113-20 PMID: 2337798
  34. Markers for biogenic amines in the aged rat brain: relationship to decline in spatial learning ability.
    Neurobiol Aging. 1990 Sep-Oct;11(5):507-14 PMID: 2234281
  35. Individual differences in the cognitive and neurobiological consequences of normal aging.
    Trends Neurosci. 1992 Sep;15(9):340-5 PMID: 1382333
  36. Neuronal plasticity and ageing processes in the frame of the 'Red Queen Theory'.
    Acta Physiol Scand. 1992 Aug;145(4):301-9 PMID: 1529720
  37. Insulin-like growth factors (IGFs): implications for aging.
    Psychoneuroendocrinology. 1992 Aug;17(4):335-42 PMID: 1279737
  38. Animal models of normal aging: relationship between cognitive decline and markers in hippocampal circuitry.
    Behav Brain Res. 1993 Nov 30;57(2):155-62 PMID: 7906946
  39. Cell death and neuronal recruitment in the high vocal center of adult male canaries are temporally related to changes in song.
    Proc Natl Acad Sci U S A. 1994 Aug 16;91(17):7844-8 PMID: 8058721
  40. Adult neurogenesis is regulated by adrenal steroids in the dentate gyrus.
    Neuroscience. 1994 Jul;61(2):203-9 PMID: 7969902
  41. Seasonal recruitment of hippocampal neurons in adult free-ranging black-capped chickadees.
    Proc Natl Acad Sci U S A. 1994 Nov 8;91(23):11217-21 PMID: 7972037
  42. Reactivity to novelty during youth as a predictive factor of cognitive impairment in the elderly: a longitudinal study in rats.
    Brain Res. 1994 Aug 8;653(1-2):51-6 PMID: 7982075
  43. Increased expression of type 1 insulin-like growth factor receptor messenger RNA in rat hippocampal formation is associated with aging and behavioral impairment.
    Neuroscience. 1996 May;72(2):505-18 PMID: 8737419
  44. Age-related production of new granule cells in the adult dentate gyrus.
    Neuroreport. 1995 Dec 15;6(18):2479-82 PMID: 8741746
  45. Preserved neuron number in the hippocampus of aged rats with spatial learning deficits.
    Proc Natl Acad Sci U S A. 1996 Sep 3;93(18):9926-30 PMID: 8790433
  46. More hippocampal neurons in adult mice living in an enriched environment.
    Nature. 1997 Apr 3;386(6624):493-5 PMID: 9087407
  47. Neuronal precursors of the adult rat subependymal zone persist into senescence, with no decline in spatial extent or response to BDNF.
    J Neurobiol. 1997 Jun 5;32(6):554-66 PMID: 9183737
  48. Epidermal growth factor and fibroblast growth factor-2 have different effects on neural progenitors in the adult rat brain.
    J Neurosci. 1997 Aug 1;17(15):5820-9 PMID: 9221780
  49. Genetic influence on neurogenesis in the dentate gyrus of adult mice.
    Proc Natl Acad Sci U S A. 1997 Sep 16;94(19):10409-14 PMID: 9294224
  50. Neurosteroids: deficient cognitive performance in aged rats depends on low pregnenolone sulfate levels in the hippocampus.
    Proc Natl Acad Sci U S A. 1997 Dec 23;94(26):14865-70 PMID: 9405705
  51. Experience-induced neurogenesis in the senescent dentate gyrus.
    J Neurosci. 1998 May 1;18(9):3206-12 PMID: 9547229
  52. Insulin-like growth factor-1 ameliorates age-related behavioral deficits.
    Neuroscience. 1998 Dec;87(3):559-69 PMID: 9758223
  53. Adrenalectomy increases neurogenesis but not PSA-NCAM expression in aged dentate gyrus.
    Eur J Neurosci. 1999 Apr;11(4):1479-85 PMID: 10103142
  54. Learning enhances adult neurogenesis in the hippocampal formation.
    Nat Neurosci. 1999 Mar;2(3):260-5 PMID: 10195219
  55. Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus.
    Nat Neurosci. 1999 Mar;2(3):266-70 PMID: 10195220
  56. Sex and seasonal differences in the rate of cell proliferation in the dentate gyrus of adult wild meadow voles.
    Neuroscience. 1999 Mar;89(3):955-64 PMID: 10199627
  57. Adult-generated neurons in the dentate gyrus send axonal projections to field CA3 and are surrounded by synaptic vesicles.
    J Comp Neurol. 1999 Apr 19;406(4):449-60 PMID: 10205022
  58. Estrogen stimulates a transient increase in the number of new neurons in the dentate gyrus of the adult female rat.
    J Neurosci. 1999 Jul 15;19(14):5792-801 PMID: 10407020
  59. Rapid extension of axons into the CA3 region by adult-generated granule cells.
    J Comp Neurol. 1999 Oct 11;413(1):146-54 PMID: 10464376
  60. Restoring production of hippocampal neurons in old age.
    Nat Neurosci. 1999 Oct;2(10):894-7 PMID: 10491610
  61. Running enhances neurogenesis, learning, and long-term potentiation in mice.
    Proc Natl Acad Sci U S A. 1999 Nov 9;96(23):13427-31 PMID: 10557337
  62. Neuroplasticity failure in Alzheimer's disease: bridging the gap between plaques and tangles.
    Neuron. 1999 Nov;24(3):521-9 PMID: 10595506
  63. Targeted neuronal death affects neuronal replacement and vocal behavior in adult songbirds.
    Neuron. 2000 Feb;25(2):481-92 PMID: 10719901
  64. New neurons: extraordinary evidence or extraordinary conclusion?
    Science. 2000 May 5;288(5467):771 PMID: 10809639
  65. Synaptic efficacy is commonly regulated within a nervous system and predicts individual differences in learning.
    Neuroreport. 2000 Apr 27;11(6):1253-8 PMID: 10817602
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.2334169100
Published
2003-11-25
Epub
2003-00-12
Pages
14385-90
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC283601
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.2334169100 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2