Cargando…
The role of P2X7 receptors in a rodent PCP-induced schizophrenia model
P2X7 receptors (P2X7Rs) are ligand-gated ion channels sensitive to extracellular ATP. Here we examined for the first time the role of P2X7R in an animal model of schizophrenia. Using the PCP induced schizophrenia model we show that both genetic deletion and pharmacological inhibition of P2X7Rs allev...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2016
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5099752/ https://www.ncbi.nlm.nih.gov/pubmed/27824163 http://dx.doi.org/10.1038/srep36680 |
_version_ | 1782466004619624448 |
---|---|
author | Koványi, Bence Csölle, Cecilia Calovi, Stefano Hanuska, Adrienn Kató, Erzsébet Köles, László Bhattacharya, Anindya Haller, József Sperlágh, Beáta |
author_facet | Koványi, Bence Csölle, Cecilia Calovi, Stefano Hanuska, Adrienn Kató, Erzsébet Köles, László Bhattacharya, Anindya Haller, József Sperlágh, Beáta |
author_sort | Koványi, Bence |
collection | PubMed |
description | P2X7 receptors (P2X7Rs) are ligand-gated ion channels sensitive to extracellular ATP. Here we examined for the first time the role of P2X7R in an animal model of schizophrenia. Using the PCP induced schizophrenia model we show that both genetic deletion and pharmacological inhibition of P2X7Rs alleviate schizophrenia-like behavioral alterations. In P2rx7+/+ mice, PCP induced hyperlocomotion, stereotype behavior, ataxia and social withdrawal. In P2X7 receptor deficient mice (P2rx7−/−), the social interactions were increased, whereas the PCP induced hyperlocomotion and stereotype behavior were alleviated. The selective P2X7 receptor antagonist JNJ-47965567 partly replicated the effect of gene deficiency on PCP-induced behavioral changes and counteracted PCP-induced social withdrawal. We also show that PCP treatment upregulates and increases the functional responsiveness of P2X7Rs in the prefrontal cortex of young adult animals. The amplitude of NMDA evoked currents recorded from layer V pyramidal neurons of cortical slices were slightly decreased by both genetic deletion of P2rx7 and by JNJ-47965567. PCP induced alterations in mRNA expression encoding schizophrenia-related genes, such as NR2A, NR2B, neuregulin 1, NR1 and GABA α1 subunit were absent in the PFC of young adult P2rx7−/− animals. Our findings point to P2X7R as a potential therapeutic target in schizophrenia. |
format | Online Article Text |
id | pubmed-5099752 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-50997522016-11-14 The role of P2X7 receptors in a rodent PCP-induced schizophrenia model Koványi, Bence Csölle, Cecilia Calovi, Stefano Hanuska, Adrienn Kató, Erzsébet Köles, László Bhattacharya, Anindya Haller, József Sperlágh, Beáta Sci Rep Article P2X7 receptors (P2X7Rs) are ligand-gated ion channels sensitive to extracellular ATP. Here we examined for the first time the role of P2X7R in an animal model of schizophrenia. Using the PCP induced schizophrenia model we show that both genetic deletion and pharmacological inhibition of P2X7Rs alleviate schizophrenia-like behavioral alterations. In P2rx7+/+ mice, PCP induced hyperlocomotion, stereotype behavior, ataxia and social withdrawal. In P2X7 receptor deficient mice (P2rx7−/−), the social interactions were increased, whereas the PCP induced hyperlocomotion and stereotype behavior were alleviated. The selective P2X7 receptor antagonist JNJ-47965567 partly replicated the effect of gene deficiency on PCP-induced behavioral changes and counteracted PCP-induced social withdrawal. We also show that PCP treatment upregulates and increases the functional responsiveness of P2X7Rs in the prefrontal cortex of young adult animals. The amplitude of NMDA evoked currents recorded from layer V pyramidal neurons of cortical slices were slightly decreased by both genetic deletion of P2rx7 and by JNJ-47965567. PCP induced alterations in mRNA expression encoding schizophrenia-related genes, such as NR2A, NR2B, neuregulin 1, NR1 and GABA α1 subunit were absent in the PFC of young adult P2rx7−/− animals. Our findings point to P2X7R as a potential therapeutic target in schizophrenia. Nature Publishing Group 2016-11-08 /pmc/articles/PMC5099752/ /pubmed/27824163 http://dx.doi.org/10.1038/srep36680 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ 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/ |
spellingShingle | Article Koványi, Bence Csölle, Cecilia Calovi, Stefano Hanuska, Adrienn Kató, Erzsébet Köles, László Bhattacharya, Anindya Haller, József Sperlágh, Beáta The role of P2X7 receptors in a rodent PCP-induced schizophrenia model |
title | The role of P2X7 receptors in a rodent PCP-induced schizophrenia model |
title_full | The role of P2X7 receptors in a rodent PCP-induced schizophrenia model |
title_fullStr | The role of P2X7 receptors in a rodent PCP-induced schizophrenia model |
title_full_unstemmed | The role of P2X7 receptors in a rodent PCP-induced schizophrenia model |
title_short | The role of P2X7 receptors in a rodent PCP-induced schizophrenia model |
title_sort | role of p2x7 receptors in a rodent pcp-induced schizophrenia model |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5099752/ https://www.ncbi.nlm.nih.gov/pubmed/27824163 http://dx.doi.org/10.1038/srep36680 |
work_keys_str_mv | AT kovanyibence theroleofp2x7receptorsinarodentpcpinducedschizophreniamodel AT csollececilia theroleofp2x7receptorsinarodentpcpinducedschizophreniamodel AT calovistefano theroleofp2x7receptorsinarodentpcpinducedschizophreniamodel AT hanuskaadrienn theroleofp2x7receptorsinarodentpcpinducedschizophreniamodel AT katoerzsebet theroleofp2x7receptorsinarodentpcpinducedschizophreniamodel AT koleslaszlo theroleofp2x7receptorsinarodentpcpinducedschizophreniamodel AT bhattacharyaanindya theroleofp2x7receptorsinarodentpcpinducedschizophreniamodel AT hallerjozsef theroleofp2x7receptorsinarodentpcpinducedschizophreniamodel AT sperlaghbeata theroleofp2x7receptorsinarodentpcpinducedschizophreniamodel AT kovanyibence roleofp2x7receptorsinarodentpcpinducedschizophreniamodel AT csollececilia roleofp2x7receptorsinarodentpcpinducedschizophreniamodel AT calovistefano roleofp2x7receptorsinarodentpcpinducedschizophreniamodel AT hanuskaadrienn roleofp2x7receptorsinarodentpcpinducedschizophreniamodel AT katoerzsebet roleofp2x7receptorsinarodentpcpinducedschizophreniamodel AT koleslaszlo roleofp2x7receptorsinarodentpcpinducedschizophreniamodel AT bhattacharyaanindya roleofp2x7receptorsinarodentpcpinducedschizophreniamodel AT hallerjozsef roleofp2x7receptorsinarodentpcpinducedschizophreniamodel AT sperlaghbeata roleofp2x7receptorsinarodentpcpinducedschizophreniamodel |