GABA and glutamate pathways are spatially and developmentally affected in the brain of Mecp2-deficient mice.

Proper brain functioning requires a fine-tuning between excitatory and inhibitory neurotransmission, a balance maintained through the regulation and release of glutamate and GABA. Rett syndrome (RTT) is a rare genetic disorder caused by mutations in the methyl-CpG binding protein 2 (MECP2) gene affe...

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Autores principales:	Rita El-Khoury, Nicolas Panayotis, Valérie Matagne, Adeline Ghata, Laurent Villard, Jean-Christophe Roux
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/31d664534ebb4c01af6413589fc8410f
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spelling	oai:doaj.org-article:31d664534ebb4c01af6413589fc8410f2021-11-18T08:26:22ZGABA and glutamate pathways are spatially and developmentally affected in the brain of Mecp2-deficient mice.1932-620310.1371/journal.pone.0092169https://doaj.org/article/31d664534ebb4c01af6413589fc8410f2014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24667344/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Proper brain functioning requires a fine-tuning between excitatory and inhibitory neurotransmission, a balance maintained through the regulation and release of glutamate and GABA. Rett syndrome (RTT) is a rare genetic disorder caused by mutations in the methyl-CpG binding protein 2 (MECP2) gene affecting the postnatal brain development. Dysfunctions in the GABAergic and glutamatergic systems have been implicated in the neuropathology of RTT and a disruption of the balance between excitation and inhibition, together with a perturbation of the electrophysiological properties of GABA and glutamate neurons, were reported in the brain of the Mecp2-deficient mouse. However, to date, the extent and the nature of the GABA/glutamate deficit affecting the Mecp2-deficient mouse brain are unclear. In order to better characterize these deficits, we simultaneously analyzed the GABA and glutamate levels in Mecp2-deficient mice at 2 different ages (P35 and P55) and in several brain areas. We used a multilevel approach including the quantification of GABA and glutamate levels, as well as the quantification of the mRNA and protein expression levels of key genes involved in the GABAergic and glutamatergic pathways. Our results show that Mecp2-deficient mice displayed regional- and age-dependent variations in the GABA pathway and, to a lesser extent, in the glutamate pathway. The implication of the GABA pathway in the RTT neuropathology was further confirmed using an in vivo treatment with a GABA reuptake inhibitor that significantly improved the lifespan of Mecp2-deficient mice. Our results confirm that RTT mouse present a deficit in the GABAergic pathway and suggest that GABAergic modulators could be interesting therapeutic agents for this severe neurological disorder.Rita El-KhouryNicolas PanayotisValérie MatagneAdeline GhataLaurent VillardJean-Christophe RouxPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 3, p e92169 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Rita El-Khoury Nicolas Panayotis Valérie Matagne Adeline Ghata Laurent Villard Jean-Christophe Roux GABA and glutamate pathways are spatially and developmentally affected in the brain of Mecp2-deficient mice.
description	Proper brain functioning requires a fine-tuning between excitatory and inhibitory neurotransmission, a balance maintained through the regulation and release of glutamate and GABA. Rett syndrome (RTT) is a rare genetic disorder caused by mutations in the methyl-CpG binding protein 2 (MECP2) gene affecting the postnatal brain development. Dysfunctions in the GABAergic and glutamatergic systems have been implicated in the neuropathology of RTT and a disruption of the balance between excitation and inhibition, together with a perturbation of the electrophysiological properties of GABA and glutamate neurons, were reported in the brain of the Mecp2-deficient mouse. However, to date, the extent and the nature of the GABA/glutamate deficit affecting the Mecp2-deficient mouse brain are unclear. In order to better characterize these deficits, we simultaneously analyzed the GABA and glutamate levels in Mecp2-deficient mice at 2 different ages (P35 and P55) and in several brain areas. We used a multilevel approach including the quantification of GABA and glutamate levels, as well as the quantification of the mRNA and protein expression levels of key genes involved in the GABAergic and glutamatergic pathways. Our results show that Mecp2-deficient mice displayed regional- and age-dependent variations in the GABA pathway and, to a lesser extent, in the glutamate pathway. The implication of the GABA pathway in the RTT neuropathology was further confirmed using an in vivo treatment with a GABA reuptake inhibitor that significantly improved the lifespan of Mecp2-deficient mice. Our results confirm that RTT mouse present a deficit in the GABAergic pathway and suggest that GABAergic modulators could be interesting therapeutic agents for this severe neurological disorder.
format	article
author	Rita El-Khoury Nicolas Panayotis Valérie Matagne Adeline Ghata Laurent Villard Jean-Christophe Roux
author_facet	Rita El-Khoury Nicolas Panayotis Valérie Matagne Adeline Ghata Laurent Villard Jean-Christophe Roux
author_sort	Rita El-Khoury
title	GABA and glutamate pathways are spatially and developmentally affected in the brain of Mecp2-deficient mice.
title_short	GABA and glutamate pathways are spatially and developmentally affected in the brain of Mecp2-deficient mice.
title_full	GABA and glutamate pathways are spatially and developmentally affected in the brain of Mecp2-deficient mice.
title_fullStr	GABA and glutamate pathways are spatially and developmentally affected in the brain of Mecp2-deficient mice.
title_full_unstemmed	GABA and glutamate pathways are spatially and developmentally affected in the brain of Mecp2-deficient mice.
title_sort	gaba and glutamate pathways are spatially and developmentally affected in the brain of mecp2-deficient mice.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/31d664534ebb4c01af6413589fc8410f
work_keys_str_mv	AT ritaelkhoury gabaandglutamatepathwaysarespatiallyanddevelopmentallyaffectedinthebrainofmecp2deficientmice AT nicolaspanayotis gabaandglutamatepathwaysarespatiallyanddevelopmentallyaffectedinthebrainofmecp2deficientmice AT valeriematagne gabaandglutamatepathwaysarespatiallyanddevelopmentallyaffectedinthebrainofmecp2deficientmice AT adelineghata gabaandglutamatepathwaysarespatiallyanddevelopmentallyaffectedinthebrainofmecp2deficientmice AT laurentvillard gabaandglutamatepathwaysarespatiallyanddevelopmentallyaffectedinthebrainofmecp2deficientmice AT jeanchristopheroux gabaandglutamatepathwaysarespatiallyanddevelopmentallyaffectedinthebrainofmecp2deficientmice
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GABA and glutamate pathways are spatially and developmentally affected in the brain of Mecp2-deficient mice.

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