Increasing Adult Hippocampal Neurogenesis is Sufficient to Reduce Anxiety and Depression-Like Behaviors
Open accessAbstract
Adult hippocampal neurogenesis is increased by antidepressants, and is required for some of their behavioral effects. However, it remains unclear whether expanding the population of adult-born neurons is sufficient to affect anxiety and depression-related behavior. Here, we use an inducible transgenic mouse model in which the pro-apoptotic gene Bax is deleted from neural stem cells and their progeny in the adult brain, and thereby increases adult neurogenesis. We find no effects on baseline anxiety and depression-related behavior; however, we find that increasing adult neurogenesis is sufficient to reduce anxiety and depression-related behaviors in mice treated chronically with corticosterone (CORT), a mouse model of stress. Thus, neurogenesis differentially affects behavior under baseline conditions and in a model of chronic stress. Moreover, we find no effect of increased adult hippocampal neurogenesis on hypothalamic-pituitary-adrenal (HPA) axis regulation, either at baseline or following chronic CORT administration, suggesting that increasing adult hippocampal neurogenesis can affect anxiety and depression-related behavior through a mechanism independent of the HPA axis. The use of future techniques to specifically inhibit BAX in the hippocampus could be used to augment adult neurogenesis, and may therefore represent a novel strategy to promote antidepressant-like behavioral effects.
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A few studies provide evidence that absence of neurogenesis elicits depressive-like symptoms in rodents, but most studies find that absent neurogenesis is not sufficient to induce a depressive phenotype, although it is required in mice for the behavioral effects of antidepressants.
“A few studies provide evidence that the absence of neurogenesis elicits depressive like symptoms in rodents123, 124, but most studies find that absent neurogenesis is not sufficient to induce a depressive phenotype125 although it is required in mice for the behavioral effects of antidepressants118, 126.”
From Dysregulation of adult hippocampal neuroplasticity in major depression: Pathogenesis and therapeutic implications (2022) · cites this paper as [125]
Adult neurogenesis in the hippocampus seems to provide resilience to stress-induced anxiety.
“Adult neurogenesis in the hippocampus seems to provide resilience to stress-induced anxiety (Anacker et al., 2018; Hill et al., 2015; Snyder et al., 2011).”
From Adult neurogenesis, glia, and the extracellular matrix (2019) · cites this paper as Hill et al., 2015
Adult hippocampal neurogenesis has been implicated in some anxiety- and depression-related behaviors.
“Adult neurogenesis in the hippocampus has been implicated in some anxiety- and depression-related behaviors (60; 61).”
From Perineuronal nets, inhibitory interneurons and anxiety-related ventral hippocampal neuronal oscillations are altered by early life adversity (2019) · cites this paper as [61]
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- Authors
- Hill, A. S., Sahay, A., & Hen, R.
- Affiliations
- Columbia University (US)
- Harvard University (US)
- New York State Psychiatric Institute (US)
- Corresponding author
- Sahay, Amar
- Hen, René
- Venue
- Neuropsychopharmacology
- Published
- 2015-04-02
- Volume
- 40
- Issue
- 10
- Pages
- 2368-2378
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- PMC
- PMC4538351
- OpenAlex
- W2029819292
- Cited by
- 557
- References
- 48
- Citations by year
- 2026: 25 · 2025: 38 · 2024: 55 · 2023: 59 · 2022: 68 · 2021: 63 · 2020: 69 · 2019: 52 · 2018: 37 · 2017: 45 · 2016: 35 · 2015: 11
- FWCI
- 17.16
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neuropsychopharmacology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (R01AG043688)
- National Institute of Mental Health (R00MH086615, R37MH068542, R01MH104175)
- 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
- adult hippocampal neurogenesis, anxiety-like behavior, depression-like behavior, neural stem cells, chronic corticosterone, chronic stress, hypothalamic-pituitary-adrenal axis, antidepressant mechanism, transgenic mouse model
- MeSH terms
- Doublecortin Domain Proteins, Animals, Anxiety, Bromodeoxyuridine, Corticosterone, Depression, Disease Models, Animal, Exploratory Behavior, Hippocampus, Hypothalamo-Hypophyseal System, Mice, Inbred C57BL, Mice, Transgenic, Microtubule-Associated Proteins, Neuropeptides, Pituitary-Adrenal System, Tamoxifen, bcl-2-Associated X Protein, Mice, Neurogenesis
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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