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http://hdl.handle.net/1942/30266
Title: | Cortical cells reveal APP as a new player in the regulation of GABAergic neurotransmission | Authors: | 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 |
Issue Date: | 2017 | Publisher: | NATURE PUBLISHING GROUP | Source: | Scientific reports, 7 (1) (Art N° ARTN 370) | 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. | Keywords: | Amyloid Precursor Protein;K-Cl Cotransporter;Hippocampal Synaptic Plasticity;Cation-Chloride Cotransporters;Alzheimers-Disease;Down-Syndrome;Mouse Model;Developmental Switch;Neuronal Development;Brain-Development | Document URI: | http://hdl.handle.net/1942/30266 | ISSN: | 2045-2322 | e-ISSN: | 2045-2322 | DOI: | 10.1038/s41598-017-00325-2 | ISI #: | 000425874200002 | 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/ | Category: | A2 | Type: | Journal Contribution |
Appears in Collections: | Research publications |
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