| Excitatory amino acid transporter 2 and excitatory amino acid transporter 1 negatively regulate calcium-dependent proliferation of hippocampal neural progenitor cells and are persistently upregulated after injury. | |
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MedLine Citation:
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PMID: 22092549 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Using a transgenic mouse (Mus musculus) in which nestin-expressing progenitors are labeled with enhanced green fluorescent protein, we previously characterized the expression of excitatory amino acid transporter 2 (GltI) and excitatory amino acid transporter 1 (Glast) on early neural progenitors in vivo. To address their functional role in this cell population, we manipulated their expression in P7 neurospheres isolated from the dentate gyrus. We observed that knockdown of GltI or Glast was associated with decreased bromodeoxyuridine incorporation and neurosphere formation. Moreover, we determined that both glutamate transporters regulated progenitor proliferation in a calcium-dependent and metabotropic glutamate receptor-dependent manner. To address the relevance of this in vivo, we utilized models of acquired brain injury, which are known to induce hippocampal neurogenesis. We observed that GltI and Glast were specifically upregulated in progenitors following brain injury, and that this increased expression was maintained for many weeks. Additionally, we found that recurrently injured animals with increased expression of glutamate transporters within the progenitor population were resistant to subsequent injury-induced proliferation. These findings demonstrate that GltI and Glast negatively regulate calcium-dependent proliferation in vitro and that their upregulation after injury is associated with decreased proliferation after brain trauma. |
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Authors:
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Jennifer A Gilley; Steven G Kernie |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2011-11-17 |
Journal Detail:
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Title: The European journal of neuroscience Volume: 34 ISSN: 1460-9568 ISO Abbreviation: Eur. J. Neurosci. Publication Date: 2011 Dec |
Date Detail:
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Created Date: 2011-11-29 Completed Date: 2012-04-04 Revised Date: 2012-10-09 |
Medline Journal Info:
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Nlm Unique ID: 8918110 Medline TA: Eur J Neurosci Country: France |
Other Details:
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Languages: eng Pagination: 1712-23 Citation Subset: IM |
Copyright Information:
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© 2011 The Authors. European Journal of Neuroscience © 2011 Federation of European Neuroscience Societies and Blackwell Publishing Ltd. |
Affiliation:
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Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acids
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metabolism Animals Calcium / metabolism* Cell Proliferation* Cells, Cultured Dentate Gyrus / cytology*, injuries*, physiology Excitatory Amino Acid Antagonists / metabolism Excitatory Amino Acid Transporter 1 / genetics, metabolism* Excitatory Amino Acid Transporter 2 / genetics, metabolism* Mice Mice, Transgenic Neural Stem Cells / cytology, physiology* RNA, Small Interfering / genetics, metabolism Xanthenes / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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R01 NS048192/NS/NINDS NIH HHS; R01 NS048192-05/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Amino Acids; 0/Excitatory Amino Acid Antagonists; 0/Excitatory Amino Acid Transporter 1; 0/Excitatory Amino Acid Transporter 2; 0/LY 341495; 0/RNA, Small Interfering; 0/Xanthenes; 7440-70-2/Calcium |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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