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Stress and Loss of Adult Neurogenesis Differentially Reduce Hippocampal Volume
Open accessAbstract
Background Hippocampal volume loss is a hallmark of clinical depression. Chronic stress produces volume loss in the hippocampus in humans and atrophy of CA3 pyramidal cells and suppression of adult neurogenesis in rodents. Methods To investigate the relationship between decreased adult neurogenesis and stress-induced changes on hippocampal structure and volume, we compared the effects of chronic unpredictable restraint stress and inhibition of neurogenesis in a rat pharmacogenetic model. Results Chronic unpredictable restraint stress over 4 weeks decreased total hippocampal volume, reflecting loss of volume in all hippocampal subfields and in both dorsal and ventral hippocampus. In contrast, complete inhibition of adult neurogenesis for 4 weeks led to volume reduction only in the dentate gyrus. With prolonged inhibition of neurogenesis, for 8 or 16 weeks, volume loss spread to the CA3 region, but not CA1. Combining stress and inhibition of adult neurogenesis did not have additive effects on the magnitude of volume loss but did produce a volume reduction throughout the hippocampus. One month of chronic unpredictable restraint stress and inhibition of adult neurogenesis both led to atrophy of pyramidal cell apical dendrites in dorsal CA3, and neuronal reorganization in ventral CA3. Stress significantly affected granule cell dendrites as well. Discussion The findings suggest that adult neurogenesis is required to maintain hippocampal volume but is not responsible for stress-induced volume loss.
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“Stress and glucocorticoids were identified to be the principal factors contributing to the shrinkage of dendrites and loss of spines in the hippocampus [93].”
From Chronic Stress-Associated Depressive Disorders: The Impact of HPA Axis Dysregulation and Neuroinflammation on the Hippocampus—A Mini Review (2025) · cites this paper as [93]
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“In addition to its suppressive effects on adult neurogenesis, stress causes dendritic retraction on CA3 pyramidal neurons (Schoenfeld et al., 2017; reviewed in McEwen, 2018), one of the main targets of new granule neurons.”
From Adult neurogenesis, glia, and the extracellular matrix (2019) · cites this paper as Schoenfeld et al., 2017
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Metadata
- Authors
- Schoenfeld, T. J., McCausland, H. C., Morris, H. D., Padmanaban, V., & Cameron, H. A.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Schoenfeld, Timothy J.
- ORCID
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2017-12
- Volume
- 82
- Issue
- 12
- Pages
- 914-923
- ISSN
- 0006-3223 (ISSN-L)
- PMC
- PMC5683934
- OpenAlex
- W2619025546
- Semantic Scholar
- d965b5035746d3357348c477b0e3012745e0bef6
- Cited by
- 260
- References
- 95
- Citations by year
- 2026: 19 · 2025: 25 · 2024: 24 · 2023: 35 · 2022: 30 · 2021: 42 · 2020: 32 · 2019: 26 · 2018: 24 · 2017: 3
- FWCI
- 9.84
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (Z01‐MH002784)
- National Institute of Mental Health (ZIAMH002784)
- 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
- hippocampal atrophy, adult neurogenesis, chronic stress, depression, CA3 pyramidal cells, dentate gyrus, brain reorganization, dendritic atrophy, hippocampal subfields
- MeSH terms
- Animals, Atrophy, Chronic Disease, Depression, Hippocampus, Male, Neurons, Organ Size, Restraint, Physical, Stress, Psychological, Rats, Long-Evans, Uncertainty, Adult Stem Cells, Neurogenesis, Rats, Transgenic, Neural Stem Cells
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