Antidepressants and Cdk inhibitors: Releasing the brake on neurogenesis?
Open accessAbstract
It is now clear that neurogenesis occurs in the brain of adult mammals. Many studies have attempted to establish relationships among neurogenesis, depression and the mechanism of action of antidepressant drugs. Therapeutic effects of antidepressants appear to be linked to increased neurogenesis in the hippocampus. Cdk inhibitors are expressed in multiple brain regions, presumably maintaining quiescence in differentiated neurons. Recently, the abundant expression of p21(Cip1) was found in neuroblasts and in newly developing neurons in the subgranular zone of the hippocampus, a region where adult neurogenesis occurs. Chronic treatment with the tricyclic antidepressant imipramine markedly decreased p21(Cip1) mRNA and protein levels and stimulated neurogenesis in this region. These results suggest that p21(Cip1) restrains neurogenesis in the hippocampus, and antidepressant-induced stimulation of neurogenesis might be a consequence of decreased p21(Cip1) expression, with the subsequent release of neuronal progenitor cells from the blockade of proliferation. These findings suggest the potential for new therapeutic strategies for the treatment of depression that target cell cycle proteins. However, there is a possibility that long-term stimulation of neurogenesis might exhaust the proliferation potentials of neuronal progenitors.
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The genes chosen for expression analysis have all recently been implicated in antidepressant drug action and neurogenesis.
“These genes were chosen because they have all recently been implicated in antidepressant drug action and neurogenesis.35, 36, 37, 38, 39, 12, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49”
From Antidepressants increase human hippocampal neurogenesis by activating the glucocorticoid receptor (2011) · cites this paper as [35]
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Antidepressants increase human hippocampal neurogenesis by activating the glucocorticoid receptor
Anacker, C., Zunszain, P. A., Cattaneo, A., Carvalho, L. A., Garabedian, M. J., Thuret, S., Price, J., & Pariante, C. M. (2011) · Molecular Psychiatry · doi:10.1038/mp.2011.26 · Cited by 435 · see citing works
- Authors
- Chesnokova, V., & Pechnick, R. N.
- Affiliations
- Cedars-Sinai Medical Center (US)
- Venue
- Cell Cycle
- Publisher
- Informa UK Limited
- Published
- 2008-08
- Volume
- 7
- Issue
- 15
- Pages
- 2321-2326
- ISSN
- 1538-4101 (ISSN-L)
- 1551-4005
- PMC
- PMC2879159
- OpenAlex
- W2043768203
- Cited by
- 19
- References
- 98
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 3 · 2023: 1 · 2021: 1 · 2019: 1 · 2017: 1 · 2015: 1 · 2013: 2 · 2012: 1
- FWCI
- 0.14
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cell Cycle (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Alliance for Research on Schizophrenia and Depression
- National Institutes of Health
- National Institute of Mental Health (MH079370, R21MH078037, MH078037, R21MH079988, MH 079988, R21MH079370)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- adult neurogenesis, antidepressants, cyclin-dependent kinase inhibitors, p21, imipramine, hippocampus, depression, neural progenitor cells, cell cycle regulation, subgranular zone, tricyclic antidepressants
- MeSH terms
- Animals, Antidepressive Agents, Brain, Cell Cycle, Cell Differentiation, Depression, Humans, Mammals, Neurons, Cyclin-Dependent Kinase Inhibitor Proteins, Adult Stem Cells
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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