SCIN affects synaptic development by regulating the entry of β-catenin into the nucleus, leading to core symptoms of autism spectrum disorder
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Background Autism spectrum disorder (ASD) often manifests as social interaction disorders, language development disorders and repetitive stereotyped behaviors. Aberrant development of neuronal synapses and dendritic spines is a commonly studied pathogenetic process. Scinderin (SCIN) is an important actin-binding protein that plays a crucial role in synaptic development. Methods A valproic acid (VPA)-induced ASD rat model was established. Behavioral tests, molecular detection (SCIN, Wnt/β-catenin components, PSD95, SYP), and analysis of β-catenin nuclear entry, neuron number, and dendritic spine density were performed. SCIN knockdown via AAV shRNA was used to verify its function. Results ASD rats showed reduced communication/exploration and increased anxiety. In the prefrontal cortex, SCIN, Wnt/β-catenin components, and β-catenin nuclear entry were upregulated; PSD95, SYP, neuron number, and dendritic spine density were downregulated. SCIN knockdown improved ASD-like behaviors and reversed these molecular/pathological changes. Conclusions SCIN regulates synaptic development via modulating β-catenin nuclear entry, thereby affecting ASD core symptoms. This study provides new pathogenic insights and identifies SCIN as a potential therapeutic target for ASD.
