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Inhibition of BET Proteins during Adolescence Affects Prefrontal Cortical Development: Relevance to Schizophrenia

Background: The present study investigated the role of proteins from the bromodomain and extra-terminal (BET) family in schizophrenia-like abnormalities in a neurodevelopmental model of schizophrenia induced by prenatal methylazoxymethanol (MAM) administration (MAM-E17). Methods: An inhibitor of BET...

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Autores principales: Bilecki, Wiktor, Wawrzczak-Bargieła, Agnieszka, Majcher-Maślanka, Iwona, Chmelova, Magdalena, Maćkowiak, Marzena
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8395847/
https://www.ncbi.nlm.nih.gov/pubmed/34445411
http://dx.doi.org/10.3390/ijms22168710
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author Bilecki, Wiktor
Wawrzczak-Bargieła, Agnieszka
Majcher-Maślanka, Iwona
Chmelova, Magdalena
Maćkowiak, Marzena
author_facet Bilecki, Wiktor
Wawrzczak-Bargieła, Agnieszka
Majcher-Maślanka, Iwona
Chmelova, Magdalena
Maćkowiak, Marzena
author_sort Bilecki, Wiktor
collection PubMed
description Background: The present study investigated the role of proteins from the bromodomain and extra-terminal (BET) family in schizophrenia-like abnormalities in a neurodevelopmental model of schizophrenia induced by prenatal methylazoxymethanol (MAM) administration (MAM-E17). Methods: An inhibitor of BET proteins, JQ1, was administered during adolescence on postnatal days (P) 23–P29, and behavioural responses (sensorimotor gating, recognition memory) and prefrontal cortical (mPFC) function (long-term potentiation (LTP), molecular and proteomic analyses) studies were performed in adult males and females. Results: Deficits in sensorimotor gating and recognition memory were observed only in MAM-treated males. However, adolescent JQ1 treatment affected animals of both sexes in the control but not MAM-treated groups and reduced behavioural responses in both sexes. An electrophysiological study showed LTP impairments only in male MAM-treated animals, and JQ1 did not affect LTP in the mPFC. In contrast, MAM did not affect activity-dependent gene expression, but JQ1 altered gene expression in both sexes. A proteomic study revealed alterations in MAM-treated groups mainly in males, while JQ1 affected both sexes. Conclusions: MAM-induced schizophrenia-like abnormalities were observed only in males, while adolescent JQ1 treatment affected memory recognition and altered the molecular and proteomic landscape in the mPFC of both sexes. Thus, transient adolescent inhibition of the BET family might prompt permanent alterations in the mPFC.
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spelling pubmed-83958472021-08-28 Inhibition of BET Proteins during Adolescence Affects Prefrontal Cortical Development: Relevance to Schizophrenia Bilecki, Wiktor Wawrzczak-Bargieła, Agnieszka Majcher-Maślanka, Iwona Chmelova, Magdalena Maćkowiak, Marzena Int J Mol Sci Article Background: The present study investigated the role of proteins from the bromodomain and extra-terminal (BET) family in schizophrenia-like abnormalities in a neurodevelopmental model of schizophrenia induced by prenatal methylazoxymethanol (MAM) administration (MAM-E17). Methods: An inhibitor of BET proteins, JQ1, was administered during adolescence on postnatal days (P) 23–P29, and behavioural responses (sensorimotor gating, recognition memory) and prefrontal cortical (mPFC) function (long-term potentiation (LTP), molecular and proteomic analyses) studies were performed in adult males and females. Results: Deficits in sensorimotor gating and recognition memory were observed only in MAM-treated males. However, adolescent JQ1 treatment affected animals of both sexes in the control but not MAM-treated groups and reduced behavioural responses in both sexes. An electrophysiological study showed LTP impairments only in male MAM-treated animals, and JQ1 did not affect LTP in the mPFC. In contrast, MAM did not affect activity-dependent gene expression, but JQ1 altered gene expression in both sexes. A proteomic study revealed alterations in MAM-treated groups mainly in males, while JQ1 affected both sexes. Conclusions: MAM-induced schizophrenia-like abnormalities were observed only in males, while adolescent JQ1 treatment affected memory recognition and altered the molecular and proteomic landscape in the mPFC of both sexes. Thus, transient adolescent inhibition of the BET family might prompt permanent alterations in the mPFC. MDPI 2021-08-13 /pmc/articles/PMC8395847/ /pubmed/34445411 http://dx.doi.org/10.3390/ijms22168710 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Bilecki, Wiktor
Wawrzczak-Bargieła, Agnieszka
Majcher-Maślanka, Iwona
Chmelova, Magdalena
Maćkowiak, Marzena
Inhibition of BET Proteins during Adolescence Affects Prefrontal Cortical Development: Relevance to Schizophrenia
title Inhibition of BET Proteins during Adolescence Affects Prefrontal Cortical Development: Relevance to Schizophrenia
title_full Inhibition of BET Proteins during Adolescence Affects Prefrontal Cortical Development: Relevance to Schizophrenia
title_fullStr Inhibition of BET Proteins during Adolescence Affects Prefrontal Cortical Development: Relevance to Schizophrenia
title_full_unstemmed Inhibition of BET Proteins during Adolescence Affects Prefrontal Cortical Development: Relevance to Schizophrenia
title_short Inhibition of BET Proteins during Adolescence Affects Prefrontal Cortical Development: Relevance to Schizophrenia
title_sort inhibition of bet proteins during adolescence affects prefrontal cortical development: relevance to schizophrenia
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8395847/
https://www.ncbi.nlm.nih.gov/pubmed/34445411
http://dx.doi.org/10.3390/ijms22168710
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