Inhibition of BET Proteins during Adolescence Affects Prefrontal Cortical Development: Relevance to Schizophrenia.
Adolescent
Adolescent Development
/ drug effects
Animals
Azepines
/ administration & dosage
Disease Models, Animal
Female
Gene Expression Regulation, Developmental
/ drug effects
Humans
Long-Term Potentiation
/ drug effects
Male
Methylazoxymethanol Acetate
/ analogs & derivatives
Prefrontal Cortex
/ drug effects
Proteomics
Rats
Recognition, Psychology
/ drug effects
Schizophrenia
/ chemically induced
Sex Characteristics
Triazoles
/ administration & dosage
JQ1
bromodomain
cognition
learning and memory
neurodevelopment
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
13 Aug 2021
13 Aug 2021
Historique:
received:
09
07
2021
revised:
06
08
2021
accepted:
09
08
2021
entrez:
27
8
2021
pubmed:
28
8
2021
medline:
22
9
2021
Statut:
epublish
Résumé
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). 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. 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. 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.
Sections du résumé
BACKGROUND
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
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
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
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.
Identifiants
pubmed: 34445411
pii: ijms22168710
doi: 10.3390/ijms22168710
pmc: PMC8395847
pii:
doi:
Substances chimiques
(+)-JQ1 compound
0
Azepines
0
Triazoles
0
Methylazoxymethanol Acetate
592-62-1
methylazoxymethanol
JGG19N3YDQ
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Narodowym Centrum Nauki
ID : 2018/31/B/NZ/014654
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