Abnormal neuronal morphology and altered synaptic proteins are restored by oxytocin in autism-related SHANK3 deficient model. (1st December 2020)

• Record Type: Journal Article
• Authors: Reichova, Alexandra; Bacova, Zuzana; Bukatova, Stanislava; Kokavcova, Martina; Meliskova, Veronika; Frimmel, Karel; Ostatnikova, Daniela; Bakos, Jan
• Is Part Of: Molecular and cellular endocrinology. Volume 518(2020)
• Publication Date: 2020-12-01
• Subjects: Autism -- SHANK3 -- Oxytocin -- Neurexins -- Neuroligins -- Development; Endocrinology -- Periodicals; Molecular biology -- Periodicals; Cytology -- Periodicals; Endocrinology -- Periodicals; Hormones -- Periodicals; Endocrinologie -- Périodiques; Cytology; Endocrinology; Molecular biology; Periodicals; 573.4
• DOI: 10.1016/j.mce.2020.110924
• Languages: English
• ISSNs: 0303-7207

Abstract

Abstract: 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. Graphical abstract: Image 1 Highlights: Oxytocin ameliorates altered neurite outgrowth in SHANK3 deficient mice. Oxytocin contributes to the regulation of synaptic proteins in conditions of SHANK3 deficiency. The action of oxytocin is accompanied by change of Rho GTPases levels.