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Cited by 103Neurogenesis and neuroplasticity mechanismsNeuroscience and Neuropharmacology ResearchMemory and Neural Mechanisms

The DOI matches its Crossref record; 60 of the 60 references it cites were found in a registry or an index.

p21 Cip1 restricts neuronal proliferation in the subgranular zone of the dentate gyrus of the hippocampus

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Pechnick, Robert N., Zonis, Svetlana, Wawrowsky, Kolja, Pourmorady, Jonathan, Chesnokova, Vera·2008·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.0711030105PMC PMC2234143
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Abstract

The subgranular zone (SGZ) of the dentate gyrus of the hippocampus is a brain region where robust neurogenesis continues throughout adulthood. Cyclin-dependent kinases (CDKs) have a primary role in controlling cell division and cellular proliferation. p21 Cip1 (p21) is a CDK inhibitor that restrains cell cycle progression. Confocal microscopy revealed that p21 is abundantly expressed in the nuclei of cells in the SGZ and is colocalized with NeuN, a marker for neurons. Doublecortin (DCX) is a cytoskeletal protein that is primarily expressed by neuroblasts. By using FACS analysis it was found that, among DCX-positive cells, 42.8% stained for p21, indicating that p21 is expressed in neuroblasts and in newly developing neurons. p21-null ( p21 −/− ) mice were examined, and the rate of cellular proliferation, as measured by BrdU incorporation, was increased in the SGZ of p21 −/− compared with WT mice. In addition, the levels of both DCX and NeuN protein were increased in p21 −/− mice, further demonstrating increased hippocampal neuron proliferation. Chronic treatment with the tricyclic antidepressant imipramine (10 mg/kg per day i.p. for 21 days) markedly decreased hippocampal p21 mRNA and protein levels, produced antidepressant-like behavioral changes in the forced swim test, and stimulated neurogenesis in the hippocampus. These results suggest that p21 restrains neurogenesis in the SGZ and imipramine-induced stimulation of neurogenesis might be a consequence of decreased p21 expression and the subsequent release of neuronal progenitor cells from the blockade of proliferation. Because many antidepressants stimulate neurogenesis, it is possible that their shared common mechanism of action is suppression of p21.

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Metadata

Authors
Pechnick, R. N., Zonis, S., Wawrowsky, K., Pourmorady, J., & Chesnokova, V.
Affiliations
  • Cedars-Sinai Medical Center (US)
  • Department of Medicine, Division of Endocrinology, and
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2008-01-29
Volume
105
Issue
4
Pages
1358-1363
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.0711030105
PMC
PMC2234143
OpenAlex
W2050238055
Cited by
103
References
60
Citations by year
2025: 2 · 2024: 3 · 2023: 2 · 2022: 1 · 2021: 4 · 2020: 7 · 2019: 5 · 2018: 7 · 2017: 9 · 2016: 6 · 2015: 9 · 2014: 7 · 2013: 10 · 2012: 3
FWCI
2.85
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institute of Mental Health (R21MH079988, MH 079988)
Topics
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
Keywords
p21 Cip1, subgranular zone, dentate gyrus, adult neurogenesis, neuronal proliferation, cyclin-dependent kinase inhibitors, neuroblasts, doublecortin, imipramine, antidepressant mechanism, forced swim test, hippocampus, cell cycle regulation
MeSH terms
Doublecortin Protein, Animals, Female, Growth Inhibitors, Male, Mice, Transgenic, Neural Inhibition, Neurons, Mice, Knockout, Gene Expression Regulation, Developmental, Dentate Gyrus, Cell Proliferation, Cyclin-Dependent Kinase Inhibitor p21, Mice

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