Suppressed proliferation and apoptotic changes in the rat dentate gyrus after acute and chronic stress are reversible
Abstract
Acute stress suppresses new cell birth in the hippocampus in several species. Relatively little is known, however, on how chronic stress affects the turnover, i.e. proliferation and apoptosis, of the rat dentate gyrus (DG) cells, and whether the stress effects are lasting. We investigated how 3 weeks of chronic unpredictable stress would influence the structural dynamic plasticity of the rat DG, and studied newborn cell proliferation, survival, apoptosis, volume and cell number in 10‐week‐old animals. To study lasting effects, another group of animals was allowed to recover for 3 weeks. Based on two independent parameters, bromodeoxyuridine (BrdU) and Ki‐67 immunocytochemistry, our results show that both chronic and acute stress decrease new cell proliferation rate. The reduced proliferation after acute stress normalized within 24 h. Interestingly, chronically stressed animals showed recovery after 3 weeks, albeit with still fewer proliferating cells than controls. Apoptosis, by contrast, increased after acute but decreased after chronic stress. These results demonstrate that, although chronic stress suppresses proliferation and apoptosis, 3 weeks of recovery again normalized most of these alterations. This may have important implications for our understanding of the reversibility of stress‐related hippocampal volume changes, such as occur, for example, in depression.
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There was no evidence from TUNEL staining that IL-1β and/or acute stress elicit hippocampal cell death either in vitro or in vivo.
“In the present study, there was no evidence from TUNEL staining that IL-1β and/or acute stress elicit hippocampal cell death either in vitro or in vivo, which is consistent with previous studies (40–42), although there is one report that severe acute stress increases apoptosis (43).”
From IL-1β is an essential mediator of the antineurogenic and anhedonic effects of stress (2008) · cites this paper as [43]
Cites
Gerdes, J., Lemke, H., Baisch, H., Wacker, H. H., Schwab, U., & Stein, H. (1984) · The Journal of Immunology · doi:10.4049/jimmunol.133.4.1710 · Cited by 4,173 · see citing works
Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus
van Praag, H., Kempermann, G., & Gage, F. H. (1999) · Nature Neuroscience · doi:10.1038/6368 · Cited by 3,880 · see citing works
West, M. J., Slomianka, L., & Gundersen, H. J. G. (1991) · The Anatomical Record · doi:10.1002/ar.1092310411 · Cited by 2,994 · see citing works
The stressed hippocampus, synaptic plasticity and lost memories
Kim, J. J., & Diamond, D. M. (2002) · Nature Reviews Neuroscience · doi:10.1038/nrn849 · Cited by 1,543 · see citing works
The cellular neurobiology of depression
Manji, H. K., Drevets, W. C., & Charney, D. S. (2001) · Nature Medicine · doi:10.1038/87865 · Cited by 1,182 · see citing works
Lemaire, V., Koehl, M., Le Moal, M., & Abrous, D. N. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.20.11032 · Cited by 1,044 · see citing works
Conrad, C. D., Magariños, A. M., LeDoux, J. E., & McEwen, B. S. (1999) · Behavioral Neuroscience · doi:10.1037/0735-7044.113.5.902 · Cited by 664 · see citing works
A two-trial memory task with automated recording: study in young and aged rats
Dellu, F., Mayo, W., Cherkaoui, J., Le Moal, M., & Simon, H. (1992) · Brain Research · doi:10.1016/0006-8993(92)91352-f · Cited by 390 · see citing works
Neural circuits mediating stress
López, J. F., Akil, H., & Watson, S. J. (1999) · Biological Psychiatry · doi:10.1016/s0006-3223(99)00266-8 · Cited by 373 · see citing works
Stress inhibits the proliferation of granule cell precursors in the developing dentate gyrus
Tanapat, P., Galea, L. A. M., & Gould, E. (1998) · International Journal of Developmental Neuroscience · doi:10.1016/s0736-5748(98)00029-x · Cited by 330 · see citing works
Alfarez, D. N., Joëls, M., & Krugers, H. J. (2003) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.2003.02622.x · Cited by 258 · see citing works
Self-citationGould, E., Woolley, C. S., & McEwen, B. S. (1991) · Journal of Comparative Neurology · doi:10.1002/cne.903130308 · Cited by 254 · see citing works
Kole, M. H. P., Swan, L., & Fuchs, E. (2002) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.2002.02136.x · Cited by 181 · see citing works
Leverenz, J. B., Wilkinson, C. W., Wamble, M., Corbin, S., Grabber, J. E., Raskind, M. A., & Peskind, E. R. (1999) · The Journal of Neuroscience · doi:10.1523/jneurosci.19-06-02356.1999 · Cited by 154 · see citing works
New neurons in old brains: learning to survive?
Greenough, W. T., Cohen, N. J., & Juraska, J. M. (1999) · Nature Neuroscience · doi:10.1038/6300 · Cited by 106 · see citing works
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Stress and the brain: from adaptation to disease
de Kloet, E. R., Joëls, M., & Holsboer, F. (2005) · Nature Reviews Neuroscience · doi:10.1038/nrn1683 · Cited by 4,621 · see citing works
Self-citationThe stress system in the human brain in depression and neurodegeneration
Swaab, D. F., Bao, A.-M., & Lucassen, P. J. (2005) · Ageing Research Reviews · doi:10.1016/j.arr.2005.03.003 · Cited by 984 · see citing works
Self-citationAdult neurogenesis: from precursors to network and physiology
Abrous, D. N., Koehl, M., & Le Moal, M. (2005) · Physiological Reviews · doi:10.1152/physrev.00055.2003 · Cited by 971 · see citing works
IL-1β is an essential mediator of the antineurogenic and anhedonic effects of stress
Koo, J. W., & Duman, R. S. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0708092105 · Cited by 862 · see citing works
Mirescu, C., & Gould, E. (2006) · Hippocampus · doi:10.1002/hipo.20155 · Cited by 701 · see citing works
The Role of Neural Plasticity in Depression: From Hippocampus to Prefrontal Cortex
Liu, W., Ge, T., Leng, Y., Pan, Z., Fan, J., Yang, W., & Cui, R. (2017) · Neural Plasticity · doi:10.1155/2017/6871089 · Cited by 640 · see citing works
Physical exercise prevents age-related decline in precursor cell activity in the mouse dentate gyrus
Kronenberg, G., Bick-Sander, A., Bunk, E., Wolf, C., Ehninger, D., & Kempermann, G. (2006) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2005.09.016 · Cited by 477 · see citing works
Chronic stress: Implications for neuronal morphology, function and neurogenesis
Joëls, M., Karst, H., Krugers, H. J., & Lucassen, P. J. (2007) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2007.04.001 · Cited by 381 · see citing works
Self-citationEffects of Chronic Stress on Structure and Cell Function in Rat Hippocampus and Hypothalamus
Joëls, M., Karst, H., Alfarez, D., Heine, V. M., Qin, Y., Riel, E. V., Verkuyl, M., Lucassen, P. J., & Krugers, H. J. (2004) · Stress · doi:10.1080/10253890500070005 · Cited by 330 · see citing works
Self-citationAdult neuroplasticity: more than 40 years of research
Fuchs, E., & Flügge, G. (2014) · Neural Plasticity · doi:10.1155/2014/541870 · Cited by 325 · see citing works
Adult hippocampal neurogenesis is functionally important for stress-induced social avoidance
Lagace, D. C., Donovan, M. H., DeCarolis, N. A., Farnbauch, L. A., Malhotra, S., Berton, O., Nestler, E. J., Krishnan, V., & Eisch, A. J. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0910072107 · Cited by 314 · see citing works
Petrik, D., Lagace, D. C., & Eisch, A. J. (2012) · Neuropharmacology · doi:10.1016/j.neuropharm.2011.09.003 · Cited by 241 · see citing works
Heine, V. M., Zareno, J., Maslam, S., Joëls, M., & Lucassen, P. J. (2005) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2005.03951.x · Cited by 225 · see citing works
Self-citationStewart, M. G., Davies, H. A., Sandi, C., Kraev, I. V., Rogachevsky, V. V., Peddie, C. J., Rodriguez, J. J., Cordero, M. I., Donohue, H. S., Gabbott, P. L. A., et al. (2005) · Neuroscience · doi:10.1016/j.neuroscience.2004.10.031 · Cited by 197 · see citing works
Early-life stress mediated modulation of adult neurogenesis and behavior
Korosi, A., Naninck, E. F. G., Oomen, C. A., Schouten, M., Krugers, H., Fitzsimons, C., & Lucassen, P. J. (2012) · Behavioural Brain Research · doi:10.1016/j.bbr.2011.07.037 · Cited by 194 · see citing works
Self-citationThe touchscreen operant platform for testing working memory and pattern separation in rats and mice.
Oomen, C. A., Hvoslef-Eide, M., Heath, C. J., Mar, A. C., Horner, A. E., Bussey, T. J., & Saksida, L. M. (2013) · Nature Protocols · doi:10.1038/nprot.2013.124 · Cited by 193 · see citing works
Opposite effects of early maternal deprivation on neurogenesis in male versus female rats
Oomen, C. A., Girardi, C. E. N., Cahyadi, R., Verbeek, E. C., Krugers, H., Joëls, M., & Lucassen, P. J. (2009) · PLoS ONE · doi:10.1371/journal.pone.0003675 · Cited by 190 · see citing works
Self-citationLucassen, P. J., Oomen, C. A., Naninck, E. F. G., Fitzsimons, C. P., van Dam, A.-M., Czeh, B., & Korosi, A. (2015) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a021303 · Cited by 166 · see citing works
GABAA receptor-acting neurosteroids: a role in the development and regulation of the stress response
Gunn, B. G., Cunningham, L., Mitchell, S. G., Swinny, J. D., Lambert, J. J., & Belelli, D. (2015) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2014.06.001 · Cited by 149 · see citing works
Guo, J.-Y., Li, C.-Y., Ruan, Y.-P., Sun, M., Qi, X.-L., Zhao, B.-S., & Luo, F. (2009) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2009.03.076 · Cited by 148 · see citing works
Conway‐Campbell, B. L., Sarabdjitsingh, R. A., McKenna, M. A., Pooley, J. R., Kershaw, Y. M., Meijer, O. C., De Kloet, E. R., & Lightman, S. L. (2010) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2010.02051.x · Cited by 137 · see citing works
Saaltink, D.-J., & Vreugdenhil, E. (2014) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-014-1568-5 · Cited by 127 · see citing works
Ganzel, B. L., Kim, P., Glover, G. H., & Temple, E. (2008) · NeuroImage · doi:10.1016/j.neuroimage.2007.12.010 · Cited by 127 · see citing works
Revsin, Y., Rekers, N. V., Louwe, M. C., Saravia, F. E., De Nicola, A. F., de Kloet, E. R., & Oitzl, M. S. (2009) · Neuropsychopharmacology · doi:10.1038/npp.2008.136 · Cited by 119 · see citing works
Dagytė, G., Van der Zee, E. A., Postema, F., Luiten, P. G. M., Den Boer, J. A., Trentani, A., & Meerlo, P. (2009) · Neuroscience · doi:10.1016/j.neuroscience.2009.05.053 · Cited by 105 · see citing works
Krugers (2010) · Frontiers in Synaptic Neuroscience · doi:10.3389/fnsyn.2010.00024 · Cited by 102 · see citing works
Adult hippocampal neurogenesis and its role in cognition.
Oomen, C. A., Bekinschtein, P., Kent, B. A., Saksida, L. M., & Bussey, T. J. (2014) · WIREs Cognitive Science · doi:10.1002/wcs.1304 · Cited by 93 · see citing works
Su, W.-J., Zhang, T., Jiang, C.-L., & Wang, W. (2018) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2018.00412 · Cited by 84 · see citing works
Klomp, A., Václavů, L., Meerhoff, G. F., Reneman, L., & Lucassen, P. J. (2014) · PLoS ONE · doi:10.1371/journal.pone.0097603 · Cited by 65 · see citing works
Self-citationKarabeg, M. M., Grauthoff, S., Kollert, S. Y., Weidner, M., Heiming, R. S., Jansen, F., Popp, S., Kaiser, S., Lesch, K.-P., Sachser, N., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0078238 · Cited by 56 · see citing works
Rodrigues, R. S., Moreira, J. B., Mateus, J. M., Barateiro, A., Paulo, S. L., Vaz, S. H., Lourenço, D. M., Ribeiro, F. F., Soares, R., Loureiro-Campos, E., et al. (2024) · Translational Psychiatry · doi:10.1038/s41398-024-02877-0 · Cited by 12 · see citing works
- Authors
- Heine, V. M., Maslam, S., Zareno, J., Joëls, M., & Lucassen, P. J.
- Affiliations
- University of Amsterdam (NL)
- Venue
- European Journal of Neuroscience
- Publisher
- Wiley
- Published
- 2003-12-16
- Volume
- 19
- Issue
- 1
- Pages
- 131-144
- ISSN
- 0953-816X (ISSN-L)
- 1460-9568
- OpenAlex
- W2063394935
- Cited by
- 317
- References
- 15
- Citations by year
- 2025: 2 · 2024: 5 · 2023: 7 · 2022: 6 · 2021: 7 · 2020: 7 · 2019: 14 · 2018: 13 · 2017: 14 · 2016: 17 · 2015: 13 · 2014: 20 · 2013: 23 · 2012: 15
- FWCI
- 3.08
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- UvA-DARE (University of Amsterdam) (publishedVersion)
- Pure Amsterdam UMC (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- National Institutes of Health
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- chronic stress, acute stress, dentate gyrus, hippocampus, neurogenesis, cell proliferation, apoptosis, stress recovery, structural plasticity, hippocampal volume, depression
- MeSH terms
- Acute Disease, Animals, Bromodeoxyuridine, Cell Division, Chronic Disease, Male, Nerve Degeneration, Neuronal Plasticity, Stress, Physiological, Rats, Wistar, Apoptosis, Dentate Gyrus, Ki-67 Antigen, Recovery of Function, Rats
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