ArticleProceedings of the National Academy of Sciences of the United States of America2008
p21Cip1 restricts neuronal proliferation in the subgranular zone of the dentate gyrus of the hippocampus.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers, 1 of them a synthesis that pooled it.
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Who cites it
60 citing papers in PubMed, 1 synthesis or guideline pooled it, 107 citations in OpenAlex.
- Pooled it
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- Cell Cycle Regulation of Hippocampal Progenitor Cells in Experimental Models of Depression and after Treatment with Fluoxetine.International journal of molecular sciences · 2021Article
- ROS Dynamics Delineate Functional States of Hippocampal Neural Stem Cells and Link to Their Activity-Dependent Exit from Quiescence.Cell stem cell · 2021Article
- Melatonin Ameliorates Valproic Acid-Induced Neurogenesis Impairment: The Role of Oxidative Stress in Adult Rats.Oxidative medicine and cellular longevity · 2021Article
- Ontogeny of adult neural stem cells in the mammalian brain.Current topics in developmental biology · 2021Review
- Cyclins, Cyclin-Dependent Kinases, and Cyclin-Dependent Kinase Inhibitors in the Mouse Nervous System.Molecular neurobiology · 2020Review
- Adult Neural Stem Cells: Born to Last.Frontiers in cell and developmental biology · 2019Review
- P11 Loss-of-Function is Associated with Decreased Cell Proliferation and Neurobehavioral Disorders in Mice.International journal of biological sciences · 2019Article
- Divide or Commit - Revisiting the Role of Cell Cycle Regulators in Adult Hippocampal Neurogenesis.Frontiers in cell and developmental biology · 2019Review
- Systemic Inflammation Impairs Proliferation of Hippocampal Type 2 Intermediate Precursor Cells.Cellular and molecular neurobiology · 2018Article
- Proliferation of hippocampal progenitors relies on p27-dependent regulation of Cdk6 kinase activity.Cellular and molecular life sciences : CMLS · 2018Article
- Inflammation-induced Gro1 triggers senescence in neuronal progenitors: effects of estradiol.Journal of neuroinflammation · 2018Article
- Retinoic Acid Is Required for Neural Stem and Progenitor Cell Proliferation in the Adult Hippocampus.Stem cell reports · 2018Article
- Genetic and Epigenetic Control of CDKN1C Expression: Importance in Cell Commitment and Differentiation, Tissue Homeostasis and Human Diseases.International journal of molecular sciences · 2018Review
- Hippocampal bone morphogenetic protein signaling mediates behavioral effects of antidepressant treatment.Molecular psychiatry · 2017Article
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5 authors at 1 institution in 1 country.
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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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