Prenatal exposure to valproic acid leads to behavioral alterations and defects of synaptic proteins in the hippocampus of adolescent rats

• Autorzy: Adamczyk A. , Gassowska-Dobrowolska M. , Cieslik M. , Czapski G.A. , Jesko H. , Gewartowska M. , Frontczak-Baniewicz M.
• Języki publikacji: EN

Abstrakty

EN

Autism spectrum disorders (ASDs) are among the most common neurodevelopmental diseases characterized by impairment in communication and social interaction along with stereotyped or repetitive behaviors. Multiple studies have highlighted the involvement of synaptic proteins in the pathogenesis of ASDs. AIM(S): The aim of this study was to investigate the effect of fetal exposure to valproic acid (VPA) – a rodent model of environmentally triggered autism – on behavioral phenotype as well as gene expression of autism-associated synaptic proteins and synapse morphology in the hippocampus of adolescent rats. METHOD(S): Pregnant Wistar rats received a single intraperitoneal injection of VPA (450 mg/kg b.w.) on gestational day 12.5. Ultrasonic vocalization was analyzed in all infant rats at postnatal day (PND) 11 and anxiety‑related behavior in adolescent male offspring. At PND 52, male offspring were decapitated and the hippocampi were isolated. Transmission electron microscopy (TEM), qPCR, and immunoblotting were used to analyze synaptic structure and protein expression. RESULTS: VPA administration during pregnancy disturbed communication in neonatal rats and led to anxiety-like and repetitive behavior in adolescent animals. TEM showed synaptic pathology including nerve endings swelling, blurred and thickened synaptic cleft structure, and disruption of synaptic membranes. Ultrastructural changes were accompanied by increased expression of proteins involved in synaptic vesicle recycling and neurotransmitter release (Synaptobrevin, Synaptophysin, Synapsin‑1) and reduction in presynaptic membrane protein SNAP25 and the postsynaptic density scaffold PSD95. Changes also occurred in the expression of Shank family proteins and neuroligin 3. CONCLUSIONS: Deregulated expression of synaptic proteins could be involved in ASDs via alterations of synaptic structure/function, subsequently contributing to behavioral abnormalities. FINANCIAL SUPPORT: Supported by NSC grant 2017/25/B/NZ4/01969.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2019
• Tom: 79
• Numer: Suppl.1
• Opis fizyczny: p.XXXVIII-XXXIX

Twórcy

autor

Adamczyk A.

• Department of Cellular Signalling, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland

autor

Gassowska-Dobrowolska M.

• Department of Cellular Signalling, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland

autor

Cieslik M.

• Department of Cellular Signalling, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland

autor

Czapski G.A.

• Department of Cellular Signalling, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland

autor

Jesko H.

• Department of Cellular Signalling, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland

autor

Gewartowska M.

• Electron Microscopy Platform, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland

autor

Frontczak-Baniewicz M.

• Electron Microscopy Platform, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland