Back to Search
Start Over
Inhibition of BET Proteins during Adolescence Affects Prefrontal Cortical Development: Relevance to Schizophrenia.
- Source :
-
International journal of molecular sciences [Int J Mol Sci] 2021 Aug 13; Vol. 22 (16). Date of Electronic Publication: 2021 Aug 13. - Publication Year :
- 2021
-
Abstract
- 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).<br />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.<br />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.<br />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.
- Subjects :
- Adolescent
Adolescent Development drug effects
Animals
Azepines pharmacology
Disease Models, Animal
Female
Gene Expression Regulation, Developmental drug effects
Humans
Long-Term Potentiation drug effects
Male
Methylazoxymethanol Acetate toxicity
Prefrontal Cortex drug effects
Prefrontal Cortex metabolism
Proteomics
Rats
Recognition, Psychology drug effects
Schizophrenia chemically induced
Schizophrenia metabolism
Sex Characteristics
Triazoles pharmacology
Azepines administration & dosage
Methylazoxymethanol Acetate analogs & derivatives
Prefrontal Cortex growth & development
Schizophrenia physiopathology
Triazoles administration & dosage
Subjects
Details
- Language :
- English
- ISSN :
- 1422-0067
- Volume :
- 22
- Issue :
- 16
- Database :
- MEDLINE
- Journal :
- International journal of molecular sciences
- Publication Type :
- Academic Journal
- Accession number :
- 34445411
- Full Text :
- https://doi.org/10.3390/ijms22168710