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NMDA-receptor inhibition and oxidative stress during hippocampal maturation differentially alter parvalbumin expression and gamma-band activity

Dysfunction of parvalbumin (PV)-expressing interneurons is thought to underlie the alterations of gamma-band oscillations observed in schizophrenia. Although the pathomechanisms of this disease remain unclear, oxidative stress induced by NMDA receptor (NMDAR) hypofunction and decreased glutathione (...

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Autores principales: Hasam-Henderson, Luisa A., Gotti, Grace C., Mishto, Michele, Klisch, Constantin, Gerevich, Zoltan, Geiger, Jörg R. P., Kovács, Richard
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6015018/
https://www.ncbi.nlm.nih.gov/pubmed/29934499
http://dx.doi.org/10.1038/s41598-018-27830-2
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author Hasam-Henderson, Luisa A.
Gotti, Grace C.
Mishto, Michele
Klisch, Constantin
Gerevich, Zoltan
Geiger, Jörg R. P.
Kovács, Richard
author_facet Hasam-Henderson, Luisa A.
Gotti, Grace C.
Mishto, Michele
Klisch, Constantin
Gerevich, Zoltan
Geiger, Jörg R. P.
Kovács, Richard
author_sort Hasam-Henderson, Luisa A.
collection PubMed
description Dysfunction of parvalbumin (PV)-expressing interneurons is thought to underlie the alterations of gamma-band oscillations observed in schizophrenia. Although the pathomechanisms of this disease remain unclear, oxidative stress induced by NMDA receptor (NMDAR) hypofunction and decreased glutathione (GSH) synthesizing capacity have been shown to lead to PV-loss and aberrant oscillatory activity. However, the individual contributions of NMDAR-inhibition and GSH-depletion to the developmental alterations observed in schizophrenia are largely unknown. We therefore investigated each condition in isolation using hippocampal slice cultures wherein interneuron maturation occurs entirely in vitro. Although both treatments caused oxidative stress, NMDAR-inhibition led to an immediate reduction in gamma oscillation frequency and a delayed loss of PV. In contrast, GSH-depletion immediately decreased PV expression and increased power, without affecting frequency. Hence, although disturbances of PV-expression and gamma oscillations coexist in schizophrenia, they can arise from separate pathological processes.
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spelling pubmed-60150182018-07-06 NMDA-receptor inhibition and oxidative stress during hippocampal maturation differentially alter parvalbumin expression and gamma-band activity Hasam-Henderson, Luisa A. Gotti, Grace C. Mishto, Michele Klisch, Constantin Gerevich, Zoltan Geiger, Jörg R. P. Kovács, Richard Sci Rep Article Dysfunction of parvalbumin (PV)-expressing interneurons is thought to underlie the alterations of gamma-band oscillations observed in schizophrenia. Although the pathomechanisms of this disease remain unclear, oxidative stress induced by NMDA receptor (NMDAR) hypofunction and decreased glutathione (GSH) synthesizing capacity have been shown to lead to PV-loss and aberrant oscillatory activity. However, the individual contributions of NMDAR-inhibition and GSH-depletion to the developmental alterations observed in schizophrenia are largely unknown. We therefore investigated each condition in isolation using hippocampal slice cultures wherein interneuron maturation occurs entirely in vitro. Although both treatments caused oxidative stress, NMDAR-inhibition led to an immediate reduction in gamma oscillation frequency and a delayed loss of PV. In contrast, GSH-depletion immediately decreased PV expression and increased power, without affecting frequency. Hence, although disturbances of PV-expression and gamma oscillations coexist in schizophrenia, they can arise from separate pathological processes. Nature Publishing Group UK 2018-06-22 /pmc/articles/PMC6015018/ /pubmed/29934499 http://dx.doi.org/10.1038/s41598-018-27830-2 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Hasam-Henderson, Luisa A.
Gotti, Grace C.
Mishto, Michele
Klisch, Constantin
Gerevich, Zoltan
Geiger, Jörg R. P.
Kovács, Richard
NMDA-receptor inhibition and oxidative stress during hippocampal maturation differentially alter parvalbumin expression and gamma-band activity
title NMDA-receptor inhibition and oxidative stress during hippocampal maturation differentially alter parvalbumin expression and gamma-band activity
title_full NMDA-receptor inhibition and oxidative stress during hippocampal maturation differentially alter parvalbumin expression and gamma-band activity
title_fullStr NMDA-receptor inhibition and oxidative stress during hippocampal maturation differentially alter parvalbumin expression and gamma-band activity
title_full_unstemmed NMDA-receptor inhibition and oxidative stress during hippocampal maturation differentially alter parvalbumin expression and gamma-band activity
title_short NMDA-receptor inhibition and oxidative stress during hippocampal maturation differentially alter parvalbumin expression and gamma-band activity
title_sort nmda-receptor inhibition and oxidative stress during hippocampal maturation differentially alter parvalbumin expression and gamma-band activity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6015018/
https://www.ncbi.nlm.nih.gov/pubmed/29934499
http://dx.doi.org/10.1038/s41598-018-27830-2
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