Repeated restraint stress suppresses neurogenesis and induces biphasic PSA‐NCAM expression in the adult rat dentate gyrus
Abstract
Chronic restraint stress has been shown to induce structural remodelling throughout the interconnected dentate gyrus-CA3 fields. To find out how this stressor affects the rate of adult hippocampal neurogenesis, we subjected rats to acute or chronic restraint stress and assessed the proliferation, survival and differentiation of newly born cells in the dentate gyrus. We also examined polysialylated neural cell adhesion molecule expression, a molecule normally expressed in immature neurons and important for morphological plasticity. The results show that acute restraint stress did not change either the proliferation of dentate gyrus precursor cells or the expression of polysialylated neural cell adhesion molecule, whereas 3 weeks of chronic restraint stress suppressed proliferation by 24% and increased polysialylated neural cell adhesion molecule expression by 40%. The study was extended for an additional 3 weeks to trace the survival and development of the cells born after the initial 3 weeks of restraint. Rats subjected to 6 weeks of daily restraint stress exhibited suppressed cell proliferation and attenuated survival of the recently born cells after the extended time course, resulting in a 47% reduction of granule cell neurogenesis. Furthermore, 6 weeks of chronic stress significantly reduced the total number of granule cells by 13% and the granule cell layer volume by 5%. Expression of polysialylated neural cell adhesion molecule followed a biphasic time course, displaying a significant up-regulation after 3 weeks of daily restraint stress that was lost after 6 weeks of stress. These studies may help us understand the basis for hippocampal shrinkage and raise questions about the ultimate reversibility of the effects of chronic stress.
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Chronic restraint stress reduces dentate gyrus proliferation whereas acute restraint does not have any measurable effect.
“Chronic restraint stress is known to reduce dentate gyrus proliferation whereas acute restraint does not have any measurable effect (Pham et al., 2003).”
From Central effects of stress hormones in health and disease: understanding the protective and damaging effects of stress and stress mediators (2008) · cites this paper as Pham et al., 2003
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- Authors
- Pham, K., Nacher, J., Hof, P. R., & McEwen, B. S.
- Affiliations
- Stanford Medicine (US)
- Icahn School of Medicine at Mount Sinai (US)
- Rockefeller University (US)
- Corresponding author
- Pham, Kara
- Venue
- European Journal of Neuroscience
- Publisher
- Wiley
- Published
- 2003-02
- Volume
- 17
- Issue
- 4
- Pages
- 879-886
- ISSN
- 0953-816X (ISSN-L)
- 1460-9568
- OpenAlex
- W2159040523
- Cited by
- 657
- References
- 54
- Citations by year
- 2026: 4 · 2025: 10 · 2024: 9 · 2023: 12 · 2022: 22 · 2021: 17 · 2020: 16 · 2019: 25 · 2018: 19 · 2017: 24 · 2016: 35 · 2015: 36 · 2014: 39 · 2013: 38 · 2012: 41
- FWCI
- 8.21
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Mental Health (MH-41256, MH-58911, P50MH058911)
- National Institute of General Medical Sciences (T32GM007524, GM07524)
- 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 restraint stress, adult hippocampal neurogenesis, dentate gyrus, PSA-NCAM, granule cell proliferation, cell survival
- MeSH terms
- Animals, Bromodeoxyuridine, Cell Count, Cell Survival, Glial Fibrillary Acidic Protein, Immunohistochemistry, Male, Neurons, Phosphopyruvate Hydratase, Restraint, Physical, Sialic Acids, Stress, Physiological, Time Factors, Rats, Sprague-Dawley, Dentate Gyrus, Neural Cell Adhesion Molecule L1, Rats
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