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Characterization of the Gene Expression Profile of Human Hippocampus in Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis

One of the main putative causes of therapy refractory epilepsy in mesial temporal lobe epilepsy (MTLE) with hippocampal sclerosis is the overexpression of multidrug transporters (MDTs) at the blood-brain barrier (BBB). It steps up the removal of antiepileptic drugs (AEDs) out of the brain cells acro...

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Autores principales: Lachos, Julio, Zattoni, Michela, Wieser, Heinz-Gregor, Fritschy, Jean-Marc, Langmann, Thomas, Schmitz, Gerd, Errede, Mariella, Virgintino, Daniela, Yonekawa, Yasuhiro, Frei, Karl
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3428621/
https://www.ncbi.nlm.nih.gov/pubmed/22937234
http://dx.doi.org/10.1155/2011/758407
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author Lachos, Julio
Zattoni, Michela
Wieser, Heinz-Gregor
Fritschy, Jean-Marc
Langmann, Thomas
Schmitz, Gerd
Errede, Mariella
Virgintino, Daniela
Yonekawa, Yasuhiro
Frei, Karl
author_facet Lachos, Julio
Zattoni, Michela
Wieser, Heinz-Gregor
Fritschy, Jean-Marc
Langmann, Thomas
Schmitz, Gerd
Errede, Mariella
Virgintino, Daniela
Yonekawa, Yasuhiro
Frei, Karl
author_sort Lachos, Julio
collection PubMed
description One of the main putative causes of therapy refractory epilepsy in mesial temporal lobe epilepsy (MTLE) with hippocampal sclerosis is the overexpression of multidrug transporters (MDTs) at the blood-brain barrier (BBB). It steps up the removal of antiepileptic drugs (AEDs) out of the brain cells across the BBB resulting in a low concentration of AEDs within the target cells. Some of the mechanisms of AED resistance are most likely to be genetically determined. To obtain more information about the underlying pathophysiology of intractability in epilepsy, we compared the global gene expression profile of human hippocampus and hippocampal-derived microvascular endothelial cells from MTLE with HS patients and controls. At the level of MDT, a significant up-regulation was found for ABCB1 (P-gp), ABCB2, ABCB3, and ABCB4, which was mainly related to endothelial cells. The data on the MDT were validated and extended by quantitative RT-PCR. Surprisingly, inflammatory factors such as interleukins (IL-1α, IL-1β, IL-6, and IL-18) and cytokines (TNF-α and TGF-β1) were found to be up-regulated in hippocampal parenchyma. The overexpression of P-gp, IL-1β, and IL-6 was also confirmed by immunohistochemistry (IHC). Our results suggest that complex expression changes of ABC-transporters may play a decisive role in pharmacoresistance in MTLE. Further studies on the new and unexpected overexpression of inflammatory cytokines may unlock hitherto undiscovered pathways of the underlying pathophysiology of human MTLE.
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spelling pubmed-34286212012-08-30 Characterization of the Gene Expression Profile of Human Hippocampus in Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis Lachos, Julio Zattoni, Michela Wieser, Heinz-Gregor Fritschy, Jean-Marc Langmann, Thomas Schmitz, Gerd Errede, Mariella Virgintino, Daniela Yonekawa, Yasuhiro Frei, Karl Epilepsy Res Treat Research Article One of the main putative causes of therapy refractory epilepsy in mesial temporal lobe epilepsy (MTLE) with hippocampal sclerosis is the overexpression of multidrug transporters (MDTs) at the blood-brain barrier (BBB). It steps up the removal of antiepileptic drugs (AEDs) out of the brain cells across the BBB resulting in a low concentration of AEDs within the target cells. Some of the mechanisms of AED resistance are most likely to be genetically determined. To obtain more information about the underlying pathophysiology of intractability in epilepsy, we compared the global gene expression profile of human hippocampus and hippocampal-derived microvascular endothelial cells from MTLE with HS patients and controls. At the level of MDT, a significant up-regulation was found for ABCB1 (P-gp), ABCB2, ABCB3, and ABCB4, which was mainly related to endothelial cells. The data on the MDT were validated and extended by quantitative RT-PCR. Surprisingly, inflammatory factors such as interleukins (IL-1α, IL-1β, IL-6, and IL-18) and cytokines (TNF-α and TGF-β1) were found to be up-regulated in hippocampal parenchyma. The overexpression of P-gp, IL-1β, and IL-6 was also confirmed by immunohistochemistry (IHC). Our results suggest that complex expression changes of ABC-transporters may play a decisive role in pharmacoresistance in MTLE. Further studies on the new and unexpected overexpression of inflammatory cytokines may unlock hitherto undiscovered pathways of the underlying pathophysiology of human MTLE. Hindawi Publishing Corporation 2011 2011-03-06 /pmc/articles/PMC3428621/ /pubmed/22937234 http://dx.doi.org/10.1155/2011/758407 Text en Copyright © 2011 Julio Lachos et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Lachos, Julio
Zattoni, Michela
Wieser, Heinz-Gregor
Fritschy, Jean-Marc
Langmann, Thomas
Schmitz, Gerd
Errede, Mariella
Virgintino, Daniela
Yonekawa, Yasuhiro
Frei, Karl
Characterization of the Gene Expression Profile of Human Hippocampus in Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis
title Characterization of the Gene Expression Profile of Human Hippocampus in Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis
title_full Characterization of the Gene Expression Profile of Human Hippocampus in Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis
title_fullStr Characterization of the Gene Expression Profile of Human Hippocampus in Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis
title_full_unstemmed Characterization of the Gene Expression Profile of Human Hippocampus in Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis
title_short Characterization of the Gene Expression Profile of Human Hippocampus in Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis
title_sort characterization of the gene expression profile of human hippocampus in mesial temporal lobe epilepsy with hippocampal sclerosis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3428621/
https://www.ncbi.nlm.nih.gov/pubmed/22937234
http://dx.doi.org/10.1155/2011/758407
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