Glucocorticoids Orchestrate Divergent Effects on Mood through Adult Neurogenesis
Open accessAbstract
Both social defeat stress and environmental enrichment stimulate adrenal glucocorticoid secretion, but they have opposing effects on hippocampal neurogenesis and mood. Hypothalamic-pituitary-adrenal axis dysregulation and decreased neurogenesis are consequences of social defeat. These outcomes are correlated with depressive states, but a causal role in the etiology of depression remains elusive. The antidepressant actions of environmental enrichment are neurogenesis-dependent, but the contribution of enrichment-elevated glucocorticoids is unexplored. Importantly, for both social defeat and environmental enrichment, how glucocorticoids interact with neurogenesis to alter mood is unknown. Here, we investigate causal roles of glucocorticoids and neurogenesis in induction of depressive-like behavior and its amelioration by environmental enrichment in mice. By blocking neurogenesis and surgically clamping adrenal hormone secretions, we showed that neurogenesis, via hypothalamic-pituitary-adrenal axis interactions, is directly involved in precipitating the depressive phenotype after social defeat. Mice adrenalectomized before social defeat showed enhanced behavioral resiliency and increased survival of adult-born hippocampal neurons compared with sham-operated defeated mice. However, mice lacking hippocampal neurogenesis did not show protective effects of adrenalectomy. Moreover, glucocorticoids secreted during environmental enrichment promoted neurogenesis and were required for restoration of normal behavior after social defeat. The data demonstrate that glucocorticoid-dependent declines in neurogenesis drive changes in mood after social defeat and that glucocorticoids secreted during enrichment promote neurogenesis and restore normal behavior after defeat. These data provide new evidence for direct involvement of neurogenesis in the etiology of depression, suggesting that treatments promoting neurogenesis can enhance stress resilience.
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Increased corticosterone has also been associated with the impaired hippocampal neurogenesis and neuronal development in the context of psychological stress.
“Increased corticosterone has also been associated with the impaired hippocampal neurogenesis and neuronal development in the context of psychological stress (Lehmann et al, 2013;McKim et al, 2016).”
From Microglia Priming with Aging and Stress (2017) · cites this paper as Lehmann et al, 2013
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- Authors
- Lehmann, M. L., Brachman, R. A., Martinowich, K., Schloesser, R. J., & Herkenham, M.
- Affiliations
- National Institutes of Health (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2013-02-13
- Volume
- 33
- Issue
- 7
- Pages
- 2961-2972
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC3711562
- OpenAlex
- W1989145093
- Cited by
- 168
- References
- 75
- Citations by year
- 2026: 9 · 2025: 4 · 2024: 7 · 2023: 6 · 2022: 7 · 2021: 15 · 2020: 13 · 2019: 9 · 2018: 18 · 2017: 16 · 2016: 20 · 2015: 16 · 2014: 18 · 2013: 10
- FWCI
- 7.91
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Mental Health (ZIAMH002832)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (T32HD007430)
- 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
- glucocorticoids, adult neurogenesis, hippocampus, social defeat stress, environmental enrichment, depression, mood, hypothalamic-pituitary-adrenal axis, adrenalectomy, behavioral resilience, antidepressant effects, stress resilience
- MeSH terms
- Adaptation, Psychological, Adrenalectomy, Affect, Animals, Antimetabolites, Behavior, Animal, Bromodeoxyuridine, Corticosterone, Depression, Environment, Glucocorticoids, Housing, Animal, Mice, Inbred C57BL, Social Behavior, Social Dominance, Stress, Psychological, Mice, Neurogenesis, Resilience, Psychological
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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