Document Detail


Altered expression of brain monocarboxylate transporter 1 in models of temporal lobe epilepsy.
MedLine Citation:
PMID:  21856423     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Monocarboxylate transporter 1 (MCT1) facilitates the transport of monocarboxylate fuels (lactate, pyruvate and ketone bodies) and acidic drugs, such as valproic acid, across cell membranes. We recently reported that MCT1 is deficient on microvessels in the epileptogenic hippocampal formation in patients with medication-refractory temporal lobe epilepsy (TLE). To further define the role of MCT1 in the pathophysiology of TLE, we used immunohistochemistry and stereological analysis to localize and quantify the transporter in the hippocampal formation in three novel and highly relevant rat models of TLE and in nonepileptic control animals. One model utilizes methionine sulfoximine to induce brain glutamine synthetase deficiency and recurrent limbic seizures, while two models employ an episode of perforant pathway stimulation to cause epilepsy. MCT1 was lost on microvessels and upregulated on astrocytes in the hippocampal formation in all models of TLE. Notably, the loss of MCT1 on microvessels was not due to a reduction in microvessel density. The similarities in MCT1 expression among human subjects with TLE and several animal models of the disease strongly suggest a critical role of this molecule in the pathogenesis of TLE. We hypothesize that the downregulation of MCT1 may promote seizures via impaired uptake of ketone bodies and antiepileptic drugs by the epileptogenic brain. We also propose that the overexpression of MCT1 on astrocytes may lead to increased uptake or release of monocarboxylates by these cells, with important implications for brain metabolism and excitability. These hypotheses can now be rigorously tested in several animal models that replicate key features of human TLE.
Authors:
Fredrik Lauritzen; Edgar L Perez; Eric R Melillo; Jung-Min Roh; Hitten P Zaveri; Tih-Shih W Lee; Yue Wang; Linda H Bergersen; Tore Eid
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-08-10
Journal Detail:
Title:  Neurobiology of disease     Volume:  45     ISSN:  1095-953X     ISO Abbreviation:  Neurobiol. Dis.     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2011-11-28     Completed Date:  2012-07-23     Revised Date:  2014-05-16    
Medline Journal Info:
Nlm Unique ID:  9500169     Medline TA:  Neurobiol Dis     Country:  United States    
Other Details:
Languages:  eng     Pagination:  165-76     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Elsevier Inc. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Animals
Astrocytes / metabolism*
Brain / metabolism*
Disease Models, Animal
Epilepsy, Temporal Lobe / genetics,  metabolism*
Male
Microvessels / metabolism
Monocarboxylic Acid Transporters / genetics,  metabolism*
Rats
Rats, Sprague-Dawley
Symporters / genetics,  metabolism*
Grant Support
ID/Acronym/Agency:
K08 NS058674/NS/NINDS NIH HHS; NS058674/NS/NINDS NIH HHS; R01 NS070824/NS/NINDS NIH HHS; UL1 RR024139/RR/NCRR NIH HHS; UL1 RR024139/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/Monocarboxylic Acid Transporters; 0/Symporters; 0/monocarboxylate transport protein 1
Comments/Corrections

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