p21Cip1 restricts neuronal proliferation in the subgranular zone of the dentate gyrus of the hippocampus.

p21Cip1 restricts neuronal proliferation in the subgranular zone of the dentate gyrus of the hippocampus. Research Abstract Details 

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p21Cip1 restricts neuronal proliferation in the subgranular zone of the dentate gyrus of the hippocampus. Abstract Text:

Robert N Pechnick,Svetlana Zonis,Kolja Wawrowsky,Jonathan Pourmorady,Vera Chesnokova,

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.

p21Cip1 restricts neuronal proliferation in the subgranular zone of the dentate gyrus of the hippocampus. Publishing Authors By Initials

RN Pechnick,S Zonis,K Wawrowsky,J Pourmorady,V Chesnokova,

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p21Cip1 restricts neuronal proliferation in the subgranular zone of the dentate gyrus of the hippocampus. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Proceedings of the National Academy of Sciences of

VOLUME: 105

Page Numbers: 1358-63

Journal Abbreviation: Proc. Natl. Acad. Sci. U.S.A.

ISSN: 1091-6490

DAY: 2

MONTH: 01

YEAR: 2008

p21Cip1 restricts neuronal proliferation in the subgranular zone of the dentate gyrus of the hippocampus. Information

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LANGUAGE: eng

NlmUniqueID: 7505876

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Grant and Affiliation Information for p21Cip1 restricts neuronal proliferation in the subgranular zone of the dentate gyrus of the hippocampus.

AFFILIATION: Department of Medicine, Division of Endocrinology, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA 90048, USA.

Country: United States

AGENCY: United States NIMH

GRANT: MH 079988

ACRONYM: MH

MEDLINETA: Proc Natl Acad Sci U S A

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