| Seizures increase cell proliferation in the dentate gyrus by shortening progenitor cell-cycle length. | |
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MedLine Citation:
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PMID: 19674059 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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PURPOSE: A prolonged seizure, status epileptics (SE), is a potent stimulus for increased neurogenesis in the dentate gyrus of the hippocampus. Molecular mechanisms that regulate normal and pathologic cell birth in the dentate gyrus are poorly understood. METHODS: Lithium-pilocarpine was used to induce SE in immature postnatal day 20 rats. Newborn cells in the dentate were labeled with bromo-deoxyuridine to determine a time-course of cell proliferation, and measure cell-cycle length. In addition, we studied expression by Western blot and immunohistochemistry of two known inhibitors of G(1)-S cell-cycle progression P27/Kip1 and P15/Ink4b following SE. RESULTS: Cell proliferation in the dentate gyrus increases starting 2 h after SE and is sustained for 40 days. Increased cell proliferation following SE is associated with a shortened dentate gyrus progenitor's cell cycle, 15 h in control to 12 h in the SE animals. To identify molecules responsible for the shortened progenitor cell cycle we studied inhibitors of cell-cycle progression P27/Kip1, and P15/Ink4b. We find decreased phosphorylation at P27/Kip1 Serine 10 and Threonine 187 following SE. Although total P27/Kip1 and P15/Ink4b levels were not altered after SE, P27/Kip1 immunoreactivity was minimal in newborn but increased with maturation of the dentate granule neurons. DISCUSSION: The sustained increase in dentate gyrus cell proliferation following SE provides a large pool of immature dentate granule cells prior to development of spontaneous seizures. A decrease in cell-cycle length of dentate gyrus progenitors is at least partially responsible for increased numbers of newborn cells following SE. |
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Authors:
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Florence P Varodayan; Xin-Jian Zhu; Xiao-Nan Cui; Brenda E Porter |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2009-08-08 |
Journal Detail:
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Title: Epilepsia Volume: 50 ISSN: 1528-1167 ISO Abbreviation: Epilepsia Publication Date: 2009 Dec |
Date Detail:
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Created Date: 2009-12-21 Completed Date: 2010-01-20 Revised Date: 2011-05-10 |
Medline Journal Info:
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Nlm Unique ID: 2983306R Medline TA: Epilepsia Country: United States |
Other Details:
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Languages: eng Pagination: 2638-47 Citation Subset: IM |
Affiliation:
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Division of Neurology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Animals, Newborn Cell Cycle / physiology Cell Proliferation Dentate Gyrus / physiology* Hippocampus Humans Immunohistochemistry Lithium Neurons Pilocarpine Status Epilepticus / physiopathology* Stem Cells / physiology |
| Grant Support | |
ID/Acronym/Agency:
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HD26979/HD/NICHD NIH HHS; K08 NS044869/NS/NINDS NIH HHS; K08 NS044869-05/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
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7439-93-2/Lithium; 92-13-7/Pilocarpine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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