mS-11, a mimetic of the mSin3-binding helix in NRSF, ameliorates social interaction deficits in a prenatal valproic acid-induced autism mouse model.
Animals
Autistic Disorder
/ chemically induced
Behavior, Animal
/ drug effects
Dendritic Spines
/ drug effects
Disease Models, Animal
Female
Heterocyclic Compounds, 2-Ring
/ administration & dosage
Interpersonal Relations
Male
Mice
Mice, Inbred ICR
Pregnancy
Prenatal Exposure Delayed Effects
/ chemically induced
RNA, Messenger
/ genetics
Repressor Proteins
/ genetics
Somatosensory Cortex
/ metabolism
Valproic Acid
/ pharmacology
Autism mouse model
NSRF
Social interaction
Valproic acid
mS-11
Journal
Pharmacology, biochemistry, and behavior
ISSN: 1873-5177
Titre abrégé: Pharmacol Biochem Behav
Pays: United States
ID NLM: 0367050
Informations de publication
Date de publication:
01 2019
01 2019
Historique:
received:
22
10
2018
revised:
07
11
2018
accepted:
08
11
2018
pubmed:
13
11
2018
medline:
26
2
2020
entrez:
13
11
2018
Statut:
ppublish
Résumé
Growing evidence suggests pivotal roles for epigenetic mechanisms in both animal models of and individuals with autism spectrum disorders (ASD). Neuron-restrictive silencer factor (NRSF) binds to neuron-restrictive silencing elements in neuronal genes and recruits co-repressors, such as mSin3, to epigenetically inhibit neuronal gene expression. Because dysregulation of NRSF is related to ASD, here we examined the effects of mS-11, a chemically optimized mimetic of the mSin3-binding helix in NRSF, on the behavioral and morphological abnormalities found in a mouse model of valproic acid (VPA)-induced ASD. Chronic treatment with mS-11 improved prenatal VPA-induced deficits in social interaction. Additionally, we found that NRSF mRNA expression was greater in the somatosensory cortex of VPA-exposed mice than of controls. Agreeing with these behavioral findings, mice that were prenatally exposed to VPA showed lower dendritic spine density in the somatosensory cortex, which was reversed by chronic treatment with mS-11. These findings suggest that mS-11 has the potential for improving ASD-related symptoms through inhibition of mSin3-NRSF binding.
Identifiants
pubmed: 30419271
pii: S0091-3057(18)30552-5
doi: 10.1016/j.pbb.2018.11.003
pii:
doi:
Substances chimiques
Heterocyclic Compounds, 2-Ring
0
MS-11 compound
0
RE1-silencing transcription factor
0
RNA, Messenger
0
Repressor Proteins
0
Valproic Acid
614OI1Z5WI
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1-5Informations de copyright
Copyright © 2018 Elsevier Inc. All rights reserved.