Skip to main content
SpringerLink
Log in

Environmentally induced long-term structural changes: Cues for functional orientation and vulnerabilities

  • Published:
Neurotoxicity Research Aims and scope Submit manuscript

Abstract

Environmental challenges profoundly modify phenotypes and disrupt inherent developmental programs both at functional and structural levels. As an example, we have studied the impact of these environmental influences on adult neurogenesis in the dentate gyrus. Neurogenesis results from an inherent program, participates to hippocampal network organization and, as a consequence, to the various functional abilities depending on this region, including memories. In preclinical studies of aging we have shown that phenotypes vulnerable to the development of spatial memory disorders are characterized by lower hippocampal neurogenesis. We have hypothesized that these interindividual variations in functional expression of neurogenesis in senescent subjects could be predicted early in life. Indeed, a behavioral response (novelty-induced locomotor reactivity) and a biological trait (hypothalamo-pituitary-adrenal axis activity), which are predictive of cognitive impairments later in life, are related to neurogenesis in young adult rats. This suggests that subjects starting off with an impaired neurogenesis, here rats that are high reactive to stress, are predisposed for the development of age-related cognitive disorders. We have further shown that these interindividual differences result from early deleterious life events. Indeed, prenatal stress orients neurogenesis in pathological ways for the entire life, and precipitates age-related cognitive impairments. Altogether these data suggest first that hippocampal neurogenesis plays a pivotal role in environmentally-induced vulnerability to the development of pathological aging, and second that environmental challenges and life events orient structural developments, leading to different phenotypes.

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.

Institutional subscriptions

Similar content being viewed by others

References

  • Abrous DN, M Koehl and M Le Moal (In Press) Adult neurogenesis, from precursors to network and physiology.Physiol. Rev. In press.

  • Adamec RE and T Shallow (1993) Lasting effects on rodent anxiety of a single exposure to a cat.Physiol. Behav. 54, 101–109.

    Article  PubMed  CAS  Google Scholar 

  • Akana SF, J Shinsako and MF Dallman (1983) Drug-induced adrenal hypertrophy provides evidence for reset in the adrenocortical system.Endocrinology 113, 2232–2237.

    Article  PubMed  CAS  Google Scholar 

  • Altman J (1962) Are new neurones formed in the brains of adult mammals?Science 135, 1127–1128.

    Article  PubMed  CAS  Google Scholar 

  • Ambrogini P, L Orsini, C Mancini, P Ferri, I Barbanti and R Cuppini (2002) Persistently high corticosterone levels but not normal circadian fluctuations of the hormone affect cell proliferation in the adult rat dentate gyrus.Neuroendocrinology 76, 366–372.

    Article  PubMed  CAS  Google Scholar 

  • Antelman SM, AJ Eichler, CA Black and D Kocan (1980) Interchangeability of stress and amphetamine in sensitization.Science 207, 329–331.

    Article  PubMed  CAS  Google Scholar 

  • Anthony JC (2001) The promise of psychiatric enviromics.Br. J. Psychiatry 178, 8S-11S.

    Article  Google Scholar 

  • Bouchard TJ Jr and JC Loehlin (2001) Genes, evolution, and personality.Behav. Genet. 31, 243–273.

    Article  PubMed  Google Scholar 

  • Bunney WE, BG Bunney, MP Vawter, H Tomita, J Li, SJ Evans, PV Choudary, RM Myers, EG Jones, SJ Watson and H Akil (2003) Microarray technology, a review of new strategies to discover candidate vulnerability genes in psychiatric disorders.Am. J. Psychiatry 160, 657–666.

    Article  PubMed  Google Scholar 

  • Cabib S, C Orsini, M Le Moal and PV Piazza (2000) Abolition and reversal of strain differences in behavioral responses to drugs of abuse after a brief experience.Science 289, 463–465.

    Article  PubMed  CAS  Google Scholar 

  • Cameron HA and E Gould (1994) Adult neurogenesis is regulated by adrenal steroids in the dentate gyrus.Neuroscience 61, 203–209.

    Article  PubMed  CAS  Google Scholar 

  • Cameron HA, P Tanapat and E Gould (1997) Adrenal steroids and N-methyl-D-aspartate receptor activation regulate neurogenesis in the dentate gyrus of adult rats through a common pathway.Neuroscience 82, 349–354.

    Article  Google Scholar 

  • Celerier E, JP Laulin, JB Corcuff, M Le Moal and G Simonnet (2001) Progressive enhancement of delayed hyperalgesia induced by repeated heroin administration, a sensitization process.J. Neurosci. 21, 4074–4080.

    PubMed  CAS  Google Scholar 

  • Charney DS, EJ Nestler and BS Bunney (1999)Neurobiology of Mental Illness (Oxford University Press: New York).

    Google Scholar 

  • Cicchetti D and TD Cannon (1999) Neurodevelopmental processes in the ontogenesis and epigenesis of psychopathology.Dev. Psychopathol. 11, 375–393.

    Article  PubMed  CAS  Google Scholar 

  • Crabbe JC, D Wahlsten and BC Dudek (1999) Genetics of mouse behavior, interactions with laboratory environment.Science 284, 1670–1672.

    Article  PubMed  CAS  Google Scholar 

  • Cutting J (1997)Principles of Psychopathology (Oxford Medical Publ: New York).

    Google Scholar 

  • Dayer AG, AA Ford, KM Cleaver, M Yassaee and HA Cameron (2003) Short-term and long-term survival of new neurons in the rat dentate gyrus.J. Comp. Neurol. 460, 563–572.

    Article  PubMed  Google Scholar 

  • Dellu F, W Mayo, M Vallee, M Le Moal and H Simon (1994) Reactivity to novelty during youth as a predictive factor of cognitive impairment in the elderly, a longitudinal study in rats.Brain Res. 653, 51–56.

    Article  PubMed  CAS  Google Scholar 

  • Dellu F, W Mayo, M Vallee, S Maccari, PV Piazza, M Le Moal and H Simon (1996) Behavioral reactivity to novelty during youth as a predictive factor of stress-induced corticosterone secretion in the elderly-a life-span study in rats.Psychoneuroendocrinology 21, 441–453.

    Article  PubMed  CAS  Google Scholar 

  • Denenberg VH (2000) Evolution proposes and ontogeny disposes.Brain Lang. 73, 274–296.

    Article  PubMed  CAS  Google Scholar 

  • Döbrössy MDE, C Aurousseau, M Le Moal, PV Piazza and DN Abrous (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 

  • Drapeau E, W Mayo, C Aurousseau, M Le Moal, PV Piazza and DN Abrous (2003) Spatial memory performances of aged rats in the water maze predict levels of hipppocampal neurogenesis.Proc. Natl. Acad. Sci. USA 100, 14385–14390.

    Article  PubMed  CAS  Google Scholar 

  • Endl E, C Hollmann and J Gerdes (2001) Antibodies against the Ki-67 protein,assessment of the growth fraction and tools for cell cycle analysis, In,Methods in Cell Biology (Academic Press: New York, NY), pp 399–418.

    Google Scholar 

  • Falconer EM and LA Galea LA (2003) Sex differences in cell proliferation, cell death and defensive behavior following acute predator odor stress in adult rats.Brain Res. 975, 22–36.

    Article  PubMed  CAS  Google Scholar 

  • Gage FH, KS Chen, G Buzsaki and D Armstrong (1988) Experimental approaches to age-related cognitive impairments.Neurobiol. Aging 9, 645–655.

    Article  PubMed  CAS  Google Scholar 

  • Gallagher M and MM Nicolle (1993) Animal models of normal aging, relationship between cognitive decline and markers in hippocampal circuitry.Behav. Brain Res. 57, 155–162.

    Article  PubMed  CAS  Google Scholar 

  • Ghaemi SN (2003)The Concepts of Psychiatry, a Pluralistic Approach to the Mind and Mental Illness (The Johns Hopkins University Press: Baltimore, MD).

    Google Scholar 

  • Glantz MD and JL Johnson (1999) Resilience and development, positive life adaptations, InLongitudinal Research in the Social and Behavioral Sciences (Kluwer Academic/Plenum Publishers: New York).

    Google Scholar 

  • Goldberg D (2001) Vulnerability factors for common mental illnesses.Br. J. Psychiatry 178, 69S-71S.

    Article  Google Scholar 

  • Gould E, HA Cameron, DC Daniels, CS Woolley and BS McEwen (1992) Adrenal hormones suppress cell division in the adult rat dentate gyrus.J. Neurosci. 12, 3642–3650.

    PubMed  CAS  Google Scholar 

  • Gross CG (2000) Neurogenesis in the adult brain, death of a dogma.Nat. Rev. Neurosci. 1, 67–73.

    Article  PubMed  CAS  Google Scholar 

  • Hastings NB and E Gould (1999) Rapid extension of axons into the CA3 region by adult-generated granule cells.J. Comp. Neurol. 413, 146–154.

    Article  PubMed  CAS  Google Scholar 

  • Heim C and CB Nemeroff (2001) The role of childhood trauma in the neurobiology of mood and anxiety disorders, preclinical and clinical studies.Biol. Psychiatry 49, 1023–1039.

    Article  PubMed  CAS  Google Scholar 

  • Heim C, PM Plotsky and CB Nemeroff (2004) Importance of studying the contributions of early adverse experience to neurobiological findings in depression.Neuropsychopharmacology 29, 641–648.

    Article  PubMed  Google Scholar 

  • Hellsten J, M Wennström, P Mohapel, CT Ekdahl, J Bengzon and A Tingström (2002) Electroconvulsive seizures increase hippocampal neurogenesis after chronic corticosterone treatment.Eur. J. Neurosci. 16, 283–290.

    Article  PubMed  Google Scholar 

  • Hyman SE (1999) Introduction to the complex genetics of mental disorders.Biol. Psychiatry 45, 518–521.

    Article  PubMed  CAS  Google Scholar 

  • Issa AM, W Rowe, S Gauthier and MJ Meaney (1990) Hypothalamic-pituitary-adrenal activity in aged, cognitively impaired and cognitively unimpaired rats.J. Neurosci. 10, 3247–3254.

    PubMed  CAS  Google Scholar 

  • Kempermann G, HG Kuhn and FH Gage (1997) More hippocampal neurons in adult mice living in an enriched environment. Nature386, 493–495.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Koehl M, V Lemaire, W Mayo, DN Abrous, S Maccari, PV Piazza, M Le Moal and M Vallee (2002) Individual vulnerability to substance abuse and affective disorders, role of early environmental influences.Neurotoxicity Res. 4, 281–296.

    Article  Google Scholar 

  • Koolhaas JM, P Meerlo, SF De Boer, JH Strubbe and B Bohus (1997) The temporal dynamics of the stress response.Neurosci. Biobehav. Rev. 21, 775–782.

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Landfield PW, JC Waymire and G Lynch (1978) Hippocampal aging and adrenocorticoids, quantitative correlations.Science 202, 1098–1102.

    Article  PubMed  CAS  Google Scholar 

  • Landfield PW, RK Baskin and TA Pitler (1981) Brain aging correlates, retardation by hormonal-pharmacological treatments.Science 214, 581–584.

    Article  PubMed  CAS  Google Scholar 

  • Larcher A, JP Laulin, E Celerier, M Le Moal and G Simonnet (1998) Acute tolerance associated with a single opiate administration, involvement of N-methyl-D-aspartate-dependent pain facilitatory systems.Neuroscience 84, 583–589.

    Article  PubMed  CAS  Google Scholar 

  • Laulin JP, A Larcher, E Celerier, M Le Moal and G Simonnet (1998) Long-lasting increased pain sensitivity in rat following exposure to heroin for the first time.Eur. J. Neurosci. 10, 782–785.

    Article  PubMed  CAS  Google Scholar 

  • Laulin JP, E Celerier, A Larcher, M Le Moal and G Simonnet (1999) Opiate tolerance to daily heroin administration, an apparent phenomenon associated with enhanced pain sensitivity.Neuroscience 89, 631–636.

    Article  PubMed  CAS  Google Scholar 

  • Lemaire V, GT Taylor and P Mormede (1997) Adrenal axis activation by chronic social stress fails to inhibit gonadal function in male rats.Psychoneuroendocrinology 22, 563–573.

    Article  PubMed  CAS  Google Scholar 

  • Lemaire V, C Aurousseau, M Le Moal and DN Abrous (1999) Behavioural trait of reactivity to novelty is related to hippocampal neurogenesis.Eur. J. Neurosci. 11, 4006–4014.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Leshner AI (1999) Science is revolutionizing our view of addiction - and what to do about it.Am. J. Psychiatry 156, 1–3.

    PubMed  CAS  Google Scholar 

  • Liu S, J Wang, D Zhu, Y Fu, K Lukowiak and YM Lu (2003) Generation of functional inhibitory neurons in the adult rat hippocampus.J. Neurosci. 23, 732–736.

    PubMed  Google Scholar 

  • Lupien SJ, M de Leon, S de Santi, A Convit, C Tarshish, NP Nair, M Thakur, BS McEwen, RL Hauger and MJ Meaney (1998) Cortisol levels during human aging predict hippocampal atrophy and memory deficits.Nat. Neurosci. 1, 69–73.

    Article  PubMed  CAS  Google Scholar 

  • Madsen TM, PE Kristjansen, TG Bolwig and G Wortwein (2003) Arrested neuronal proliferation and impaired hippocampal function following fractionated brain irradiation in the adult rat.Neuroscience 119, 635–642.

    Article  PubMed  CAS  Google Scholar 

  • Markakis EA and FH Gage (1999) Adult-generated neurons in the dentate gyrus send axonal projections to field CA3 and are surrounded by synaptic vesicles.J. Comp. Neurol. 406, 449–460.

    Article  PubMed  CAS  Google Scholar 

  • Markowska AL, WS Stone, DK Ingram, J Reynolds, PE Gold, LH Conti, MJ Pontecorvo, GL Wenk and DS Olton (1989) Individual differences in aging, behavioral and neurobiological correlates.Neurobiol. Aging 10, 31–43.

    Article  PubMed  CAS  Google Scholar 

  • McEwen BS and E Stellar (1993) Stress and the individual. Mechanisms leading to disease.Arch. Intern. Med. 153, 2093–2101.

    Article  PubMed  CAS  Google Scholar 

  • McEwen BS, H Cameron, HM Chao, E Gould, AM Magarinos, Y Watanabe and CS Woolley (1993 Adrenal steroids and plasticity of hippocampal neurons, toward an understanding of underlying cellular and molecular mechanisms.Cell. Mol. Neurobiol. 13, 457–482.

    Article  PubMed  CAS  Google Scholar 

  • Meaney MJ (2001) Maternal care, gene expression, and the transmission of individual differences in stress reactivity across generations.Annu. Rev. Neurosci. 24, 1161–1192.

    Article  PubMed  CAS  Google Scholar 

  • Mesulam M-M (1999) Neuroplasticity failure in Alzheimer’s dDisease: bridging the gap between plaques and tangles.Neuron 24, 521–529.

    Article  PubMed  CAS  Google Scholar 

  • Montaron MF, PV Piazza, C Aurousseau, A Urani, M Le Moal and DN Abrous (2003) Implication of corticosteroid receptors in the regulation of hippocampal structural plasticity.Eur. J. Neurosci. 18, 3105–3111.

    Article  PubMed  CAS  Google Scholar 

  • Nowakowski RS and NL Hayes (1999) CNS development, an overview.Dev. Psychopathol. 11, 395–417.

    Article  PubMed  CAS  Google Scholar 

  • Okano HJ, DW Pfaff and RB Gibbs (1996) Expression of EGFR-, p75NGFR-, and PSTAIR (cdc2)-like immunoreactivity by proliferating cells in the adult rat hippocampal formation and fore-brain.Dev. Neurosci. 18, 199–209.

    Article  PubMed  CAS  Google Scholar 

  • Perry B, RA Pollard, TL Blackley, WL Baker and D Vigilante (1995) Childhood trauma, the neurobiology of adaptation and “use-dependent” development of the brain: how “states” become “traits”.Infant Mental Health J. 16, 271–291.

    Article  Google Scholar 

  • Post RM (1992) Transduction of psychosocial stress into the neurobiology of recurrent affective disorder.Am. J. Psychiatry 149, 999–1010.

    PubMed  CAS  Google Scholar 

  • Rapp PR and DG Amaral (1992) Individual differences in the cognitive and neurobiological consequences of normal aging.Trends Neurosci. 15, 340–345.

    Article  PubMed  CAS  Google Scholar 

  • Ritscher JEB, V Warner, JG Johnson and BP Dohrenwend (2001) Inter-generational longitudinal study of social class and depression, a test of social causation and social selection models.Cell. Mol. Neurobiol. 178, 84–97.

    Google Scholar 

  • Rodriguez JJ, MF Montaron, KG Petry, C Aurousseau, M Marinelli, S Premier, G Rougon, M Le Moal and DN Abrous (1998) Complex regulation of the expression of the polysialylated form of the neuronal cell adhesion molecule by glucocorticoids in the rat hippocampus.Eur. J. Neurosci. 10, 2994–3006.

    Article  PubMed  CAS  Google Scholar 

  • Rose S (2001) Moving on from old dichotomies: beyond nature-nurture towards a lifeline perspective.Br. J. Psychiatry 178, S3-S7.

    Article  Google Scholar 

  • Rutter ML (1999) Psychosocial adversity and child psychopathology.Br. J. Psychiatry 174, 480–493.

    Article  PubMed  CAS  Google Scholar 

  • Rutter M and J Silberg (2002) Gene environment interplay in relation to emotional and behavioral disturbances.Ann. Rev. Psychol. 53, 463–491.

    Article  Google Scholar 

  • Sapolsky RM (1992)Stress, the Aging Brain, and the Mechanisms of Neuron Death (MIT Press: Cambridge, MA).

    Google Scholar 

  • Seki T and Y Arai Y (1995) Age-related production of new granule cells in the adult dentate gyrus.Neuroreport 6, 2479–2482.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Solomon RL (1991) Acquired motiuvation and affective oppoonent processes, InNeurobiology of Learning and Affect (Madden J., Ed.) (Raven Press: New York), pp 307–347.

    Google Scholar 

  • Song HJ, CF Stevens and FH Gage (2002) Neural stem cells from adult hippocampus develop essential properties of functional CNS neurons.Nat. Neurosci. 5, 438–445.

    PubMed  CAS  Google Scholar 

  • Stam R, AW Bruijnzeel and VM Wiegant (2000) Long-lasting stress sensitisation.Eur. J. Pharmacol. 405, 217–224.

    Article  PubMed  CAS  Google Scholar 

  • Stanfield BB and JE Trice (1988) Evidence that granule cells generated in the dentate gyrus of adult rats extend axonal projections.Exp. Brain Res. 72, 399–406.

    PubMed  CAS  Google Scholar 

  • Steiner B, G Kronenberg, S Jessberger, MD Brandt, K Reuter and G Kempermann (2004) Differential regulation of gliogenesis in the context of adult hippocampal neurogenesis in mice.Glia 46, 41–52.

    Article  PubMed  Google Scholar 

  • Sterling P and J Eyer (1988) Allostasis: a new paradigm to explain arousal pathology, InHanbook of Life Stress. Cognition and Health (Fisher S and J Reason, Eds.) (Willey J & Sons Ltd: New York, NY), pp 629–649.

    Google Scholar 

  • Tanapat P, NB Hastings, TA Rydel, LA Galea and E Gould (2001) Exposure to fox odor inhibits cell proliferation in the hippocam pus of adult rats via an adrenal hormone-dependent mechanism.J. Comp. Neurol. 437, 496–504.

    Article  PubMed  CAS  Google Scholar 

  • Vallée M, W Mayo, M Darnaudéry, C Corpéchot, J Young, M Koehl, M Le Moal, EE Baulieu, P Robel and H Simon (1997) Neurosteroids, deficient cognitive performance in aged rats depends on low pregnenolone sulfate levels in the hippocampus.Proc. Natl. Acad. Sci. USA 94, 14865–14870.

    Article  PubMed  Google Scholar 

  • Vallée M, S Maccari, F Dellu, H Simon, M Le Moal and W Mayo (1999) Long-term effects of prenatal stress and postnatal handling on age-related glucocorticoid secretion and cognitive performance, a longitudinal study in the rat.Eur. J. Neurosci. 11, 2906–2916.

    Article  PubMed  Google Scholar 

  • Van Praag HM (1999) Nosologomania, a disorder in psychiatry.Tijdschrift voor Psychiatrie 41, 403–712.

    Google Scholar 

  • van Praag H, BR Christie, TJ Sejnowski and FH Gage (1999a) Running enhances neurogenesis, learning, and long-term potentiation in mice.Proc. Natl. Acad. Sci. USA 96, 13427–13431.

    Article  PubMed  Google Scholar 

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

    Article  Google Scholar 

  • van Praag H, AF Schinder, BR Christie, N Toni, TD Palmer and FH Gage (2002) Functional neurogenesis in the adult hippocampus.Nature 415, 1030–1034.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. INSERM U588, Domaine de Carreire, Rue Camille Saint Saëns, University of Bordeaux II Bordeaux, 33077, Cedex, France

    M. F. Montaron, M. Koehl, V. Lemaire, E. Drapeau, D. N. Abrous & M. Le Moal

Authors
  1. M. F. Montaron
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. Koehl
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. V. Lemaire
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. E. Drapeau
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. D. N. Abrous
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. M. Le Moal
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to D. N. Abrous.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Montaron, M.F., Koehl, M., Lemaire, V. et al. Environmentally induced long-term structural changes: Cues for functional orientation and vulnerabilities. neurotox res 6, 571–580 (2004). https://doi.org/10.1007/BF03033453

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03033453

Keywords

Search

Navigation