Cortical cells reveal APP as a new player in the regulation of GABAergic neurotransmission

Abstract The amyloid precursor protein (APP) modulates synaptic activity, resulting from the fine tuning of excitatory and inhibitory neurotransmission. GABAergic inhibitory neurotransmission is affected by modifications in intracellular chloride concentrations regulated by Na+-K+-2Cl− cotransporter...

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Autores principales:	Anna Doshina, Florian Gourgue, Michiho Onizuka, Remi Opsomer, Peng Wang, Kunie Ando, Bernadette Tasiaux, Ilse Dewachter, Pascal Kienlen-Campard, Jean-Pierre Brion, Philippe Gailly, Jean-Noël Octave, Nathalie Pierrot
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/17df00cf26f446d68bc775b9993f6c1a
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spelling	oai:doaj.org-article:17df00cf26f446d68bc775b9993f6c1a2021-12-02T16:06:54ZCortical cells reveal APP as a new player in the regulation of GABAergic neurotransmission10.1038/s41598-017-00325-22045-2322https://doaj.org/article/17df00cf26f446d68bc775b9993f6c1a2017-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00325-2https://doaj.org/toc/2045-2322Abstract The amyloid precursor protein (APP) modulates synaptic activity, resulting from the fine tuning of excitatory and inhibitory neurotransmission. GABAergic inhibitory neurotransmission is affected by modifications in intracellular chloride concentrations regulated by Na+-K+-2Cl− cotransporter 1 (NKCC1) and neuronal K+-Cl− cotransporter 2 (KCC2), allowing entrance and efflux of chloride, respectively. Modifications in NKCC1 and KCC2 expression during maturation of cortical cells induce a shift in GABAergic signaling. Here, we demonstrated that APP affects this GABA shift. Expression of APP in cortical cells decreased the expression of KCC2, without modifying NKCC1, eliciting a less inhibitory GABA response. Downregulation of KCC2 expression by APP was independent of the APP intracellular domain, but correlated with decreased expression of upstream stimulating factor 1 (USF1), a potent regulator of Slc12a5 gene expression (encoding KCC2). KCC2 was also downregulated in vivo following APP expression in neonatal mouse brain. These results argue for a key role of APP in the regulation of GABAergic neurotransmission.Anna DoshinaFlorian GourgueMichiho OnizukaRemi OpsomerPeng WangKunie AndoBernadette TasiauxIlse DewachterPascal Kienlen-CampardJean-Pierre BrionPhilippe GaillyJean-Noël OctaveNathalie PierrotNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Anna Doshina Florian Gourgue Michiho Onizuka Remi Opsomer Peng Wang Kunie Ando Bernadette Tasiaux Ilse Dewachter Pascal Kienlen-Campard Jean-Pierre Brion Philippe Gailly Jean-Noël Octave Nathalie Pierrot Cortical cells reveal APP as a new player in the regulation of GABAergic neurotransmission
description	Abstract The amyloid precursor protein (APP) modulates synaptic activity, resulting from the fine tuning of excitatory and inhibitory neurotransmission. GABAergic inhibitory neurotransmission is affected by modifications in intracellular chloride concentrations regulated by Na+-K+-2Cl− cotransporter 1 (NKCC1) and neuronal K+-Cl− cotransporter 2 (KCC2), allowing entrance and efflux of chloride, respectively. Modifications in NKCC1 and KCC2 expression during maturation of cortical cells induce a shift in GABAergic signaling. Here, we demonstrated that APP affects this GABA shift. Expression of APP in cortical cells decreased the expression of KCC2, without modifying NKCC1, eliciting a less inhibitory GABA response. Downregulation of KCC2 expression by APP was independent of the APP intracellular domain, but correlated with decreased expression of upstream stimulating factor 1 (USF1), a potent regulator of Slc12a5 gene expression (encoding KCC2). KCC2 was also downregulated in vivo following APP expression in neonatal mouse brain. These results argue for a key role of APP in the regulation of GABAergic neurotransmission.
format	article
author	Anna Doshina Florian Gourgue Michiho Onizuka Remi Opsomer Peng Wang Kunie Ando Bernadette Tasiaux Ilse Dewachter Pascal Kienlen-Campard Jean-Pierre Brion Philippe Gailly Jean-Noël Octave Nathalie Pierrot
author_facet	Anna Doshina Florian Gourgue Michiho Onizuka Remi Opsomer Peng Wang Kunie Ando Bernadette Tasiaux Ilse Dewachter Pascal Kienlen-Campard Jean-Pierre Brion Philippe Gailly Jean-Noël Octave Nathalie Pierrot
author_sort	Anna Doshina
title	Cortical cells reveal APP as a new player in the regulation of GABAergic neurotransmission
title_short	Cortical cells reveal APP as a new player in the regulation of GABAergic neurotransmission
title_full	Cortical cells reveal APP as a new player in the regulation of GABAergic neurotransmission
title_fullStr	Cortical cells reveal APP as a new player in the regulation of GABAergic neurotransmission
title_full_unstemmed	Cortical cells reveal APP as a new player in the regulation of GABAergic neurotransmission
title_sort	cortical cells reveal app as a new player in the regulation of gabaergic neurotransmission
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/17df00cf26f446d68bc775b9993f6c1a
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Cortical cells reveal APP as a new player in the regulation of GABAergic neurotransmission

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