| Glycolysis inhibition decreases the levels of glutamate transporters and enhances glutamate neurotoxicity in the R6/2 Huntington's disease mice. | |
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MedLine Citation:
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PMID: 20401690 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Excitotoxicity has been associated with the loss of medium spiny neurons (MSN) in Huntington's disease (HD). We have previously observed that the content of the glial glutamate transporters, glutamate transporter 1 (GLT-1) and glutamate-aspartate transporter (GLAST), diminishes in R6/2 mice at 14 weeks of age but not at 10 weeks, and that this change correlates with an increased vulnerability of striatal neurons to glutamate toxicity. We have also reported that inhibition of the glycolytic pathway decreases glutamate uptake and enhances glutamate neurotoxicity in the rat brain. We now show that at 10-weeks of age, glutamate excitotoxicity is precipitated in R6/2 mice, after the treatment with iodoacetate (IOA), an inhibitor of the glycolytic enzyme, glyceraldehyde-3-phosphate dehydrogenase (GAPDH). IOA induces a larger inhibition of GAPDH in R6/2 mice, while it similarly reduces the levels of GLT-1 and GLAST in wild-type and transgenic animals. Results suggest that metabolic failure and altered glutamate uptake are involved in the vulnerability of striatal neurons to glutamate excitotoxicity in HD. |
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Authors:
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Ana María Estrada-Sánchez; Teresa Montiel; Lourdes Massieu |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-04-18 |
Journal Detail:
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Title: Neurochemical research Volume: 35 ISSN: 1573-6903 ISO Abbreviation: Neurochem. Res. Publication Date: 2010 Aug |
Date Detail:
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Created Date: 2010-06-28 Completed Date: 2010-09-07 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7613461 Medline TA: Neurochem Res Country: United States |
Other Details:
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Languages: eng Pagination: 1156-63 Citation Subset: IM |
Affiliation:
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Departamento de Neuropatología Molecular, División de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico DF, Mexico. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acid Transport System X-AG
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metabolism* Animals Brain / drug effects, metabolism Female Glutamic Acid / metabolism*, toxicity Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating) / antagonists & inhibitors, metabolism Glycolysis Huntington Disease / genetics, metabolism* Iodoacetates / pharmacology Mice Mice, Inbred BALB C Mice, Transgenic |
| Chemical | |
Reg. No./Substance:
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0/Amino Acid Transport System X-AG; 0/Iodoacetates; 56-86-0/Glutamic Acid; EC 1.2.1.12/Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating) |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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