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http://hdl.handle.net/1942/30266
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DC Field | Value | Language |
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dc.contributor.author | Doshina, Anna | - |
dc.contributor.author | Gourgue, Florian | - |
dc.contributor.author | Onizuka, Michiho | - |
dc.contributor.author | Opsomer, Remi | - |
dc.contributor.author | Wang, Peng | - |
dc.contributor.author | Ando, Kunie | - |
dc.contributor.author | Tasiaux, Bernadette | - |
dc.contributor.author | DEWACHTER, Ilse | - |
dc.contributor.author | Kienlen-Campard, Pascal | - |
dc.contributor.author | Brion, Jean-Pierre | - |
dc.contributor.author | Gailly, Philippe | - |
dc.contributor.author | Octave, Jean-Noël | - |
dc.contributor.author | Pierrot, Nathalie | - |
dc.date.accessioned | 2020-01-09T11:09:37Z | - |
dc.date.available | 2020-01-09T11:09:37Z | - |
dc.date.issued | 2017 | - |
dc.date.submitted | 2020-01-09T10:15:06Z | - |
dc.identifier.citation | Scientific reports, 7 (1) (Art N° ARTN 370) | - |
dc.identifier.uri | http://hdl.handle.net/1942/30266 | - |
dc.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. | - |
dc.description.sponsorship | This work was supported by the Belgian Fonds pour la Recherche Scientifique (FNRS-FRS), Interuniversity Attraction Poles Programme-Belgian State-Belgian Science Policy (PAI/IAP), The Belgian Fonds de la Recherche Scientifique Médicale (FRSM), the Queen Elisabeth Medical Foundation (FMRE) and the Fondation pour la Recherche sur la Maladie d’Alzheimer (SAO/FRA). The T4 deposited at the DSHB by Lytle, C./Forbush III, B. (DSHB Hybridoma Product T4) is maintained at The University of Iowa, Department of Biology, Iowa City, IA 52242. We thank the Netherlands Brain Bank (NBB) for providing human brain samples. We thank Pr. T. Michiels (de Duve Institute, Brussels, Belgium) for the generous gift of pTM898neo and lentiviral packaging (gag-pol, rev, and VsVg) plasmids. We thank also J. Kerr for his help, and M. Rider for his critical reading. | - |
dc.language.iso | en | - |
dc.publisher | NATURE PUBLISHING GROUP | - |
dc.rights | The Author(s) 2017. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ | - |
dc.subject.other | Amyloid Precursor Protein | - |
dc.subject.other | K-Cl Cotransporter | - |
dc.subject.other | Hippocampal Synaptic Plasticity | - |
dc.subject.other | Cation-Chloride Cotransporters | - |
dc.subject.other | Alzheimers-Disease | - |
dc.subject.other | Down-Syndrome | - |
dc.subject.other | Mouse Model | - |
dc.subject.other | Developmental Switch | - |
dc.subject.other | Neuronal Development | - |
dc.subject.other | Brain-Development | - |
dc.title | Cortical cells reveal APP as a new player in the regulation of GABAergic neurotransmission | - |
dc.type | Journal Contribution | - |
dc.identifier.issue | 1 | - |
dc.identifier.volume | 7 | - |
local.bibliographicCitation.jcat | A2 | - |
local.publisher.place | MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND | - |
local.type.refereed | Refereed | - |
local.type.specified | Article | - |
local.bibliographicCitation.artnr | ARTN 370 | - |
dc.source.type | Article | - |
dc.identifier.doi | 10.1038/s41598-017-00325-2 | - |
dc.identifier.pmid | 28337033 | - |
dc.identifier.isi | 000425874200002 | - |
dc.identifier.eissn | 2045-2322 | - |
local.provider.type | PubMed | - |
local.uhasselt.uhpub | no | - |
item.fullcitation | Doshina, Anna; Gourgue, Florian; Onizuka, Michiho; Opsomer, Remi; Wang, Peng; Ando, Kunie; Tasiaux, Bernadette; DEWACHTER, Ilse; Kienlen-Campard, Pascal; Brion, Jean-Pierre; Gailly, Philippe; Octave, Jean-Noël & Pierrot, Nathalie (2017) Cortical cells reveal APP as a new player in the regulation of GABAergic neurotransmission. In: Scientific reports, 7 (1) (Art N° ARTN 370). | - |
item.fulltext | With Fulltext | - |
item.accessRights | Closed Access | - |
item.contributor | Doshina, Anna | - |
item.contributor | Gourgue, Florian | - |
item.contributor | Onizuka, Michiho | - |
item.contributor | Opsomer, Remi | - |
item.contributor | Wang, Peng | - |
item.contributor | Ando, Kunie | - |
item.contributor | Tasiaux, Bernadette | - |
item.contributor | DEWACHTER, Ilse | - |
item.contributor | Kienlen-Campard, Pascal | - |
item.contributor | Brion, Jean-Pierre | - |
item.contributor | Gailly, Philippe | - |
item.contributor | Octave, Jean-Noël | - |
item.contributor | Pierrot, Nathalie | - |
crisitem.journal.issn | 2045-2322 | - |
crisitem.journal.eissn | 2045-2322 | - |
Appears in Collections: | Research publications |
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