Reduction of epileptiform activity in ketogenic mice: The role of monocarboxylate transporters

Abstract Epilepsy is a chronic neurological disorder that affects approximately 50 million people worldwide. Ketogenic diet (KD) can be a very effective treatment for intractable epilepsy. Potential mechanisms of action for KD have been proposed, including the re-balance among excitatory and inhibit...

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Autores principales:	Linda S. Forero-Quintero, Joachim W. Deitmer, Holger M. Becker
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3316e60dc7a3415fb0f81630a930ad78
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spelling	oai:doaj.org-article:3316e60dc7a3415fb0f81630a930ad782021-12-02T11:52:34ZReduction of epileptiform activity in ketogenic mice: The role of monocarboxylate transporters10.1038/s41598-017-05054-02045-2322https://doaj.org/article/3316e60dc7a3415fb0f81630a930ad782017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05054-0https://doaj.org/toc/2045-2322Abstract Epilepsy is a chronic neurological disorder that affects approximately 50 million people worldwide. Ketogenic diet (KD) can be a very effective treatment for intractable epilepsy. Potential mechanisms of action for KD have been proposed, including the re-balance among excitatory and inhibitory neurotransmission and decrease in the glycolytic rate in brain cells. KD has been shown to have an effect on the expression pattern of monocarboxylate transporters (MCT), however, it is unknown whether MCT transport activity is affected by KD and linked to the reduction of seizures during KD. Therefore, we studied the influence of KD on MCT transport activity and the role of MCTs during epileptiform activity. Our results showed a decrease in the epileptiform activity in cortical slices from mice fed on KD and in the presence of beta-hydroxybutyrate. KD increased transport capacity for ketone bodies and lactate in cortical astrocytes by raising the MCT1 expression level. Inhibition of MCT1 and MCT2 in control conditions decreases epileptiform activity, while in KD it induced an increase in epileptiform activity. Our results suggest that MCTs not only play an important role in the transport of ketone bodies, but also in the modulation of brain energy metabolism under normal and ketogenic conditions.Linda S. Forero-QuinteroJoachim W. DeitmerHolger M. BeckerNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Linda S. Forero-Quintero Joachim W. Deitmer Holger M. Becker Reduction of epileptiform activity in ketogenic mice: The role of monocarboxylate transporters
description	Abstract Epilepsy is a chronic neurological disorder that affects approximately 50 million people worldwide. Ketogenic diet (KD) can be a very effective treatment for intractable epilepsy. Potential mechanisms of action for KD have been proposed, including the re-balance among excitatory and inhibitory neurotransmission and decrease in the glycolytic rate in brain cells. KD has been shown to have an effect on the expression pattern of monocarboxylate transporters (MCT), however, it is unknown whether MCT transport activity is affected by KD and linked to the reduction of seizures during KD. Therefore, we studied the influence of KD on MCT transport activity and the role of MCTs during epileptiform activity. Our results showed a decrease in the epileptiform activity in cortical slices from mice fed on KD and in the presence of beta-hydroxybutyrate. KD increased transport capacity for ketone bodies and lactate in cortical astrocytes by raising the MCT1 expression level. Inhibition of MCT1 and MCT2 in control conditions decreases epileptiform activity, while in KD it induced an increase in epileptiform activity. Our results suggest that MCTs not only play an important role in the transport of ketone bodies, but also in the modulation of brain energy metabolism under normal and ketogenic conditions.
format	article
author	Linda S. Forero-Quintero Joachim W. Deitmer Holger M. Becker
author_facet	Linda S. Forero-Quintero Joachim W. Deitmer Holger M. Becker
author_sort	Linda S. Forero-Quintero
title	Reduction of epileptiform activity in ketogenic mice: The role of monocarboxylate transporters
title_short	Reduction of epileptiform activity in ketogenic mice: The role of monocarboxylate transporters
title_full	Reduction of epileptiform activity in ketogenic mice: The role of monocarboxylate transporters
title_fullStr	Reduction of epileptiform activity in ketogenic mice: The role of monocarboxylate transporters
title_full_unstemmed	Reduction of epileptiform activity in ketogenic mice: The role of monocarboxylate transporters
title_sort	reduction of epileptiform activity in ketogenic mice: the role of monocarboxylate transporters
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/3316e60dc7a3415fb0f81630a930ad78
work_keys_str_mv	AT lindasforeroquintero reductionofepileptiformactivityinketogenicmicetheroleofmonocarboxylatetransporters AT joachimwdeitmer reductionofepileptiformactivityinketogenicmicetheroleofmonocarboxylatetransporters AT holgermbecker reductionofepileptiformactivityinketogenicmicetheroleofmonocarboxylatetransporters
_version_	1718394975729745920

Reduction of epileptiform activity in ketogenic mice: The role of monocarboxylate transporters

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