Effects of early-life tactile experience enrichment on autistic-like behaviors and synaptic alterations in Shank3 mutant mice.

Autism spectrum disorder (ASD) presents a significant therapeutic challenge due to limited treatment options. While non-pharmacological approaches based on sensory stimulation have shown promise in clinical practice, the underlying mechanisms remain poorly understood. This study explored the therapeutic potential of tactile experience enrichment (TEE) during specific developmental windows in Shank3 KO mice, a model of ASD. We found that pre-weaning TEE robustly rescued core behavioral deficits, including social interaction and repetitive grooming, whereas juvenile TEE only improved social behavior. RNA sequencing of the anterior cingulate cortex (ACC) and dorsolateral striatum (DLS) revealed TEE-induced alterations in synaptic gene expression, including the upregulation of the Polo-like kinase 1 (PLK-1) pathway, which may modulate synaptic maturation. Furthermore, pre-weaning TEE restored dendritic spine density and morphology, along with synaptic transmission, in both the ACC and DLS. These findings indicate that early tactile enrichment, particularly during the pre-weaning period, can effectively alleviate core ASD-related behaviors in Shank3 KO mice by modulating synaptic structure and function, highlighting its potential as a therapeutic intervention for ASD.