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Cited by 85Neurogenesis and neuroplasticity mechanismsMemory and Neural MechanismsAging and Gerontology Research

Stem-cell-associated structural and functional plasticity in the aging hippocampus.

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Jessberger, Sebastian, Gage, Fred H.·2008·Psychology and Aging
DOI 10.1037/a0014188PMC PMC2771615
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Abstract

Aging frequently leads to a functional decline across multiple cognitive domains, often resulting in a severe reduction in life quality and also causing substantial care-related costs. Understanding age-associated structural and functional changes of neural circuitries within the brain is required to improve successful aging. In this review, the authors focus on age-dependent alterations of the hippocampus and the decline of hippocampal function, which are critically involved in processes underlying certain forms of learning and memory. Despite the dramatic reductions in hippocampus-dependent function that accompany advancing age, there is also striking evidence that even the aged brain retains a high level of plasticity. Thus, one promising avenue to reach the goal of successful aging might be to boost and recruit this plasticity, which is the interplay between neural structure, function, and experience, to prevent age-related cognitive decline and age-associated comorbidities.

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  1. Aimone JB Wiles J Gage FH 2006 Potential role for adult neurogenesis in the encoding of time in new memories Nat Neurosci 9 6 723 727 16732202
  2. Barnes CA 1979 Memory deficits associated with senescence: a neurophysiological and behavioral study in the rat J Comp Physiol Psychol 93 1 74 104 221551
  3. Barnes CA 1994 Normal aging: regionally specific changes in hippocampal synaptic transmission Trends Neurosci 17 1 13 18 7511843
  4. Barnes CA McNaughton BL 1980 Physiological compensation for loss of afferent synapses in rat hippocampal granule cells during senescence J Physiol 309 473 485 7252877 PMC1274597
  5. Barnes CA Rao G McNaughton BL 1987 Increased electrotonic coupling in aged rat hippocampus: a possible mechanism for cellular excitability changes J Comp Neurol 259 4 549 558 2439551
  6. Becker S 2005 A computational principle for hippocampal learning and neurogenesis Hippocampus 15 6 722 738 15986407
  7. Bird CM Burgess N 2008 The hippocampus and memory: insights from spatial processing Nat Rev Neurosci 9 3 182 194 18270514
  8. Bizon JL Gallagher M 2003 Production of new cells in the rat dentate gyrus over the lifespan: relation to cognitive decline Eur J Neurosci 18 1 215 219 12859354
  9. Bizon JL Lee HJ Gallagher M 2004 Neurogenesis in a rat model of age-related cognitive decline Aging Cell 3 4 227 234 15268756
  10. Bliss TV Collingridge GL 1993 A synaptic model of memory: long-term potentiation in the hippocampus Nature 361 6407 31 39 8421494
  11. Burke SN Barnes CA 2006 Neural plasticity in the ageing brain Nat Rev Neurosci 7 1 30 40 16371948
  12. Cameron HA McKay RD 1999 Restoring production of hippocampal neurons in old age Nat Neurosci 2 10 894 897 10491610
  13. Chirumamilla S Sun D Bullock MR Colello RJ 2002 Traumatic brain injury induced cell proliferation in the adult mammalian central nervous system J Neurotrauma 19 6 693 703 12165131
  14. Churchill JD Galvez R Colcombe S Swain RA Kramer AF Greenough WT 2002 Exercise, experience and the aging brain Neurobiol Aging 23 5 941 955 12392797
  15. Cole AJ Saffen DW Baraban JM Worley PF 1989 Rapid increase of an immediate early gene messenger RNA in hippocampal neurons by synaptic NMDA receptor activation Nature 340 6233 474 476 2547165
  16. Couillard-Despres S Winner B Karl C Lindemann G Schmid P Aigner R 2006 Targeted transgene expression in neuronal precursors: watching young neurons in the old brain Eur J Neurosci 24 6 1535 1545 17004917
  17. Curcio CA Hinds JW 1983 Stability of synaptic density and spine volume in dentate gyrus of aged rats Neurobiol Aging 4 1 77 87 6877491
  18. Dieguez D Jr Barea-Rodriguez EJ 2004 Aging impairs the late phase of long-term potentiation at the medial perforant path-CA3 synapse in awake rats Synapse 52 1 53 61 14755632 PMC1913478
  19. Doetsch F Hen R 2005 Young and excitable: the function of new neurons in the adult mammalian brain Curr Opin Neurobiol 15 1 121 128 15721754
  20. Draganski B Gaser C Kempermann G Kuhn HG Winkler J Buchel C 2006 Temporal and spatial dynamics of brain structure changes during extensive learning J Neurosci 26 23 6314 6317 16763039 PMC6675198
  21. Drapeau E Mayo W Aurousseau C Le Moal M Piazza PV Abrous DN 2003 Spatial memory performances of aged rats in the water maze predict levels of hippocampal neurogenesis Proc Natl Acad Sci U S A 100 24 14385 14390 14614143 PMC283601
  22. Eriksson PS Perfilieva E Björk-Eriksson T Alborn AM Nordborg C Peterson DA 1998 Neurogenesis in the adult human hippocampus Nat Med 4 1313 1317 9809557
  23. Finkbiner RG Woodruff-Pak DS 1991 Classical eyeblink conditioning in adulthood: effects of age and interstimulus interval on acquisition in the trace paradigm Psychol Aging 6 1 109 117 2029359
  24. Flood DG Guarnaccia M Coleman PD 1987 Dendritic extent in human CA2-3 hippocampal pyramidal neurons in normal aging and senile dementia Brain Res 409 1 88 96 3580872
  25. Gage F 2000 Mammalian neural stem cells Science 287 1433 1438 10688783
  26. Gage FH Dunnett SB Bjorklund A 1984 Spatial learning and motor deficits in aged rats Neurobiol Aging 5 1 43 48 6738785
  27. Ge S Yang CH Hsu KS Ming GL Song H 2007 A Critical Period for Enhanced Synaptic Plasticity in Newly Generated Neurons of the Adult Brain Neuron 54 4 559 566 17521569 PMC2040308
  28. Geinisman Y de Toledo-Morrell L Morrell F Persina IS Rossi M 1992 Age-related loss of axospinous synapses formed by two afferent systems in the rat dentate gyrus as revealed by the unbiased stereological dissector technique Hippocampus 2 4 437 444 1308200
  29. Gould E Beylin A Tanapat P Reeves A Shors TJ 1999 Learning enhances adult neurogenesis in the hippoampal formation Nat Neurosci 2 260 265 10195219
  30. Gould E Reeves AJ Fallah M Tanapat P Gross CG Fuchs E 1999 Hippocampal neurogenesis in adult old world primates Proc Natl Acad Sci USA 96 5263 5267 10220454 PMC21852
  31. Gould E Tanapat P 1999 Stress and hippocampal neurogenesis Biol Psychiatry 46 11 1472 1479 10599477
  32. Gross CG 2000 Neurogenesis in the adult brain: death of a dogma Nat Rev Neurosci 1 1 67 73 11252770
  33. Hanks SD Flood DG 1991 Region-specific stability of dendritic extent in normal human aging and regression in Alzheimer's disease. I. CA1 of hippocampus Brain Res 540 1-2 63 82 2054634
  34. Hattiangady B Rao MS Shetty GA Shetty AK 2005 Brain-derived neurotrophic factor, phosphorylated cyclic AMP response element binding protein and neuropeptide Y decline as early as middle age in the dentate gyrus and CA1 and CA3 subfields of the hippocampus Exp Neurol 195 2 353 371 16002067
  35. Jessberger S Kempermann G 2003 Adult-born hippocampal neurons mature into activity-dependent responsiveness Eur J Neurosci 18 10 2707 2712 14656319
  36. Kandel ER 2001 The molecular biology of memory storage: a dialog between genes and synapses Biosci Rep 21 5 565 611 12168768
  37. Kempermann G 2008 The neurogenic reserve hypothesis: what is adult hippocampal neurogenesis good for Trends Neurosci 18329110
  38. Kempermann G Gast D Gage FH 2002 Neuroplasticity in old age: sustained fivefold induction of hippocampal neurogenesis by long-term environmental enrichment Ann Neurol 52 2 135 143 12210782
  39. Kempermann G Jessberger S Steiner B Kronenberg G 2004 Milestones of neuronal development in the adult hippocampus Trends Neurosci 27 8 447 452 15271491
  40. Kempermann G Kuhn HG Gage FH 1997a Genetic influence on neurogenesis in the dentate gyrus of adult mice Proc Natl Acad Sci USA 94 10409 10414 9294224 PMC23376
  41. Kempermann G Kuhn HG Gage FH 1997b More hippocampal neurons in adult mice living in an enriched environment Nature 386 493 495 9087407
  42. Kempermann G Kuhn HG Gage FH 1998 Experience-induced neurogenesis in the senescent dentate gyrus J Neurosci 18 9 3206 3212 9547229 PMC6792643
  43. Keuker JI Luiten PG Fuchs E 2003 Preservation of hippocampal neuron numbers in aged rhesus monkeys Neurobiol Aging 24 1 157 165 12493561
  44. Kishimoto Y Suzuki M Kawahara S Kirino Y 2001 Age-dependent impairment of delay and trace eyeblink conditioning in mice Neuroreport 12 15 3349 3352 11711884
  45. Kramer AF Colcombe S Erickson K Belopolsky A McAuley E Cohen NJ 2002 Effects of aerobic fitness training on human cortical function: a proposal J Mol Neurosci 19 1-2 227 231 12212786
  46. Kramer AF Hahn S Cohen NJ Banich MT McAuley E Harrison CR 1999 Ageing, fitness and neurocognitive function Nature 400 6743 418 419 10440369
  47. Kuhn HG Dickinson-Anson H Gage FH 1996 Neurogenesis in the dentate gyrus of the adult rat: age-related decrease of neuronal progenitor proliferation J Neurosci 16 6 2027 2033 8604047 PMC6578509
  48. Lai ZC Moss MB Killiany RJ Rosene DL Herndon JG 1995 Executive system dysfunction in the aged monkey: spatial and object reversal learning Neurobiol Aging 16 6 947 954 8622786
  49. Laplagne DA Esposito MS Piatti VC Morgenstern NA Zhao C van Praag H 2006 Functional convergence of neurons generated in the developing and adult hippocampus PLoS Biol 4 12 e409 17121455 PMC1637132
  50. Lee J Duan W Long JM Ingram DK Mattson MP 2000 Dietary restriction increases the number of newly generated neural cells, and induces BDNF expression, in the dentate gyrus of rats J Mol Neurosci 15 2 99 108 11220789
  51. Lendvai B Stern EA Chen B Svoboda K 2000 Experience-dependent plasticity of dendritic spines in the developing rat barrel cortex in vivo Nature 404 6780 876 881 10786794
  52. Lindsay J Laurin D Verreault R Hebert R Helliwell B Hill GB 2002 Risk factors for Alzheimer's disease: a prospective analysis from the Canadian Study of Health and Aging Am J Epidemiol 156 5 445 453 12196314
  53. Manganas LN Zhang X Li Y Hazel RD Smith SD Wagshul ME 2007 Magnetic resonance spectroscopy identifies neural progenitor cells in the live human brain Science 318 5852 980 985 17991865 PMC4039561
  54. Markham JA McKian KP Stroup TS Juraska JM 2005 Sexually dimorphic aging of dendritic morphology in CA1 of hippocampus Hippocampus 15 1 97 103 15390161
  55. Merrill DA Karim R Darraq M Chiba AA Tuszynski MH 2003 Hippocampal cell genesis does not correlate with spatial learning ability in aged rats J Comp Neurol 459 2 201 207 12640670
  56. Miller NE 1969 Psychosomatic effects of specific types of training Ann N Y Acad Sci 159 3 1025 1040 4900681
  57. Milner B Squire LR Kandel ER 1998 Cognitive neuroscience and the study of memory Neuron 20 3 445 468 9539121
  58. Ming GL Song H 2005 Adult neurogenesis in the mammalian central nervous system Annu Rev Neurosci 28 223 250 16022595
  59. Montaron MF Drapeau E Dupret D Kitchener P Aurousseau C Le Moal M 2006 Lifelong corticosterone level determines age-related decline in neurogenesis and memory Neurobiol Aging 27 4 645 654 15953661
  60. Morgan JI Cohen DR Hempstead JL Curran T 1987 Mapping patterns of c-fos expression in the central nervous system after seizure Science 237 4811 192 197 3037702
  61. Moyer JR Jr Brown TH 2006 Impaired trace and contextual fear conditioning in aged rats Behav Neurosci 120 3 612 624 16768613
  62. Parent JM Yu TW Leibowitz RT Geschwind DH Sloviter RS Lowenstein DH 1997 Dentate granule cell neurogenesis is increased by seizures and contributes to aberrant network reorganization in the adult rat hippocampus J Neurosci 17 3727 3738 9133393 PMC6573703
  63. Patrylo PR Tyagi I Willingham AL Lee S Williamson A 2007 Dentate filter function is altered in a proepileptic fashion during aging Epilepsia 48 10 1964 1978 17521341
  64. Patrylo PR Williamson A 2007 The effects of aging on dentate circuitry and function Prog Brain Res 163 679 696 17765745
  65. Piatti VC Esposito MS Schinder AF 2006 The timing of neuronal development in adult hippocampal neurogenesis Neuroscientist 12 6 463 468 17079512
  66. Plassman BL Langa KM Fisher GG Heeringa SG Weir DR Ofstedal MB 2008 Prevalence of cognitive impairment without dementia in the United States Ann Intern Med 148 6 427 434 18347351 PMC2670458
  67. Rao MS Hattiangady B Abdel-Rahman A Stanley DP Shetty AK 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 2 464 476 15673445
  68. Rao MS Hattiangady B Shetty AK 2006 The window and mechanisms of major age-related decline in the production of new neurons within the dentate gyrus of the hippocampus Aging Cell 5 6 545 558 17129216
  69. Rapp PR Heindel WC 1994 Memory systems in normal and pathological aging Curr Opin Neurol 7 4 294 298 7952236
  70. Rapp PR Kansky MT Roberts JA 1997 Impaired spatial information processing in aged monkeys with preserved recognition memory Neuroreport 8 8 1923 1928 9223078
  71. Rosenzweig ES Barnes CA 2003 Impact of aging on hippocampal function: plasticity, network dynamics, and cognition Prog Neurobiol 69 3 143 179 12758108
  72. Santarelli L Saxe M Gross C Surget A Battaglia F Dulawa S 2003 Requirement of hippocampal neurogenesis for the behavioral effects of antidepressants Science 301 5634 805 809 12907793
  73. Saxe MD Battaglia F Wang JW Malleret G David DJ Monckton JE 2006 Ablation of hippocampal neurogenesis impairs contextual fear conditioning and synaptic plasticity in the dentate gyrus Proc Natl Acad Sci U S A 103 46 17501 17506 17088541 PMC1859958
  74. Schinder AF Gage FH 2004 A hypothesis about the role of adult neurogenesis in hippocampal function Physiology (Bethesda) 19 253 261 15381753
  75. Schmidt HD Duman RS 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 17762509
  76. Schmidt-Hieber C Jonas P Bischofberger J 2004 Enhanced synaptic plasticity in newly generated granule cells of the adult hippocampus Nature 429 6988 184 187 15107864
  77. Sheperd GME 2003 The Synaptic Organization of the Brain Oxford University Press USA 5th
  78. Shetty AK Hattiangady B Shetty GA 2005 Stem/progenitor cell proliferation factors FGF-2, IGF-1, and VEGF exhibit early decline during the course of aging in the hippocampus: role of astrocytes Glia 51 3 173 186 15800930
  79. Squire LR 1992 Memory and the hippocampus: a synthesis from findings with rats, monkeys, and humans Psychol Rev 99 2 195 231 1594723 published erratum appears in Psychol Rev 1992 Jul 99 3 582
  80. Squire LR Stark CE Clark RE 2004 The medial temporal lobe Annu Rev Neurosci 27 279 306 15217334
  81. Steiner B Wolf S Kempermann G 2006 Adult neurogenesis and neurodegenerative disease Regen Med 1 1 15 28 17465817
  82. Tashiro A Makino H Gage FH 2007 Experience-specific functional modification of the dentate gyrus through adult neurogenesis: a critical period during an immature stage J Neurosci 27 12 3252 3259 17376985 PMC6672473
  83. Tashiro A Sandler VM Toni N Zhao C Gage FH 2006 NMDA-receptor-mediated, cell-specific integration of new neurons in adult dentate gyrus Nature 442 7105 929 933 16906136
  84. Thibault O Hadley R Landfield PW 2001 Elevated postsynaptic [Ca2+]i and L-type calcium channel activity in aged hippocampal neurons: relationship to impaired synaptic plasticity J Neurosci 21 24 9744 9756 11739583 PMC6763040
  85. Toni N Buchs PA Nikonenko I Bron CR Muller D 1999 LTP promotes formation of multiple spine synapses between a single axon terminal and a dendrite Nature 402 6760 421 425 10586883
  86. Van Praag H Christie BR Sejnowski TJ Gage FH 1999 Running enhances neurogenesis, learning and long-term potentiation in mice Proc Natl Acad Sci USA 96 23 13427 13431 10557337 PMC23964
  87. van Praag H Schinder AF Christie BR Toni N Palmer TD Gage FH 2002 Functional neurogenesis in the adult hippocampus Nature 415 6875 1030 1034 11875571 PMC9284568
  88. van Praag H Shubert T Zhao C Gage FH 2005 Exercise enhances learning and hippocampal neurogenesis in aged mice J Neurosci 25 38 8680 8685 16177036 PMC1360197
  89. Wang S Scott BW Wojtowicz JM 2000 Heterogenous properties of dentate granule neurons in the adult rat J Neurobiol 42 2 248 257 10640331
  90. Wilkniss SM Jones MG Korol DL Gold PE Manning CA 1997 Age-related differences in an ecologically based study of route learning Psychol Aging 12 2 372 375 9189997
  91. Williams RS Matthysse S 1986 Age-related changes in Down syndrome brain and the cellular pathology of Alzheimer disease Prog Brain Res 70 49 67 2953042
  92. Wilmoth JR 1998 The future of human longevity: a demographer's perspective Science 280 5362 395 397 9575086
  93. Wilson IA Ikonen S Gallagher M Eichenbaum H Tanila H 2005 Age-associated alterations of hippocampal place cells are subregion specific J Neurosci 25 29 6877 6886 16033897 PMC6725350
  94. Winocur G Wojtowicz JM Sekeres M Snyder JS Wang S 2006 Inhibition of neurogenesis interferes with hippocampus-dependent memory function Hippocampus 16 3 296 304 16411241
  95. Zhang CL Zou Y He W Gage FH Evans RM 2008 A role for adult TLX-positive neural stem cells in learning and behaviour Nature 451 7181 1004 1007 18235445

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Authors
Jessberger, S., & Gage, F. H.
Affiliations
  • ETH Zurich (CH)
  • Salk Institute for Biological Studies (US)
ORCID
Venue
Psychology and Aging
Publisher
American Psychological Association (APA)
Published
2008
Volume
23
Issue
4
Pages
684-691
ISSN
  • 0882-7974 (ISSN-L)
  • 1939-1498
DOI
10.1037/a0014188
PMC
PMC2771615
OpenAlex
W1988213378
Cited by
85
References
5
Citations by year
2026: 1 · 2025: 2 · 2023: 1 · 2022: 1 · 2021: 1 · 2020: 2 · 2019: 2 · 2018: 3 · 2017: 3 · 2016: 6 · 2015: 3 · 2014: 9 · 2013: 8 · 2012: 12
FWCI
3.16
Type
journal article
Language
en
Open access
Locations
  • Psychology and Aging (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institute on Aging (R01AG006088)
Topics
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
  • Social Sciences › Psychology › Neuropsychology and Physiological Psychology › Aging and Gerontology Research
Keywords
hippocampus, brain aging, neuroplasticity, structural plasticity, functional plasticity, age-related cognitive decline, successful aging, learning and memory
MeSH terms
Aged, Aging, Animals, Animals, Newborn, Cerebral Cortex, Hippocampus, Humans, Learning, Memory, Nerve Net, Neuronal Plasticity, Stem Cells, Cellular Senescence, Mice, Neurogenesis

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