Abnormal neuronal morphology and altered synaptic proteins are restored by oxytocin in autism-related SHANK3 deficient model.
Animals
Animals, Newborn
Autistic Disorder
/ genetics
Cells, Cultured
Disease Models, Animal
Female
Gene Expression
/ drug effects
Humans
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Microfilament Proteins
/ genetics
Nerve Tissue Proteins
/ genetics
Neurites
/ drug effects
Neurons
/ drug effects
Neuroprotection
/ drug effects
Oxytocin
/ pharmacology
Receptors, Neurotransmitter
/ genetics
Autism
Development
Neurexins
Neuroligins
Oxytocin
SHANK3
Journal
Molecular and cellular endocrinology
ISSN: 1872-8057
Titre abrégé: Mol Cell Endocrinol
Pays: Ireland
ID NLM: 7500844
Informations de publication
Date de publication:
01 12 2020
01 12 2020
Historique:
received:
01
04
2020
revised:
22
05
2020
accepted:
23
06
2020
pubmed:
4
7
2020
medline:
29
6
2021
entrez:
4
7
2020
Statut:
ppublish
Résumé
Oxytocin has been suggested as a potential therapeutic agent in autism and other neuropsychiatric conditions. Although, the link between the deficit in "SH3 domain and ankyrin repeat containing protein 3" (SHANK3) and autism spectrum disorders is highly studied topic, developmental mechanisms are still poorly understood. In this study, we clearly confirm that SHANK3 deficiency is accompanied with abnormalities in neurite number and length, which are reversed by oxytocin treatment (1 μM, 48h) in primary hippocampal neurons. Transient silencing for the SHANK3 gene (siSHANK3) in neuron-like cell line (SH-SY5Y) revealed a significant decrease in the expression levels of Neurexins 1α, 1β, 2α and 2β. Oxytocin treatment compensated reduced levels of Synapsin I, PSD95 and Neuroligin 3 in siSHANK3 cells suggesting a marked potential of oxytocin to ameliorate defects present in conditions of SHANK3 deficiency. Further analysis of hippocampal tissue revealed that oxytocin application (0.1 μg/μl, s.c. at P2 and P3 day) affects levels of synaptic proteins and GTPases in both WT and SHANK3 deficient mice on day P5. Oxytocin stimulated the mRNA expression of RhoB and Rac1 in both WT and SHANK3 deficient mice. Our data suggest that autism relevant synaptic pathologies could be reversed by oxytocin treatment.
Identifiants
pubmed: 32619581
pii: S0303-7207(20)30224-0
doi: 10.1016/j.mce.2020.110924
pii:
doi:
Substances chimiques
Microfilament Proteins
0
Nerve Tissue Proteins
0
Receptors, Neurotransmitter
0
Shank3 protein, mouse
0
Oxytocin
50-56-6
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
110924Informations de copyright
Copyright © 2020 Elsevier B.V. All rights reserved.