Integrin β1/FAK/SRC signal pathway is involved in autism spectrum disorder in Tspan7 knockout rats.

Abstract

TSPAN7 is related to various neurological disorders including autism spectrum disorder (ASD). However, the underlying synaptic mechanism of TSPAN7 in ASD is still unclear. Here, we showed that Tspan7 knockout rats exhibited ASD-like and ID-like behavioral phenotypes, brain structure alterations including decreased hippocampal and cortical volume, and related pathological changes including reduced hippocampal neurons number, neuronal complexity, dendritic spines, and synapse-associated proteins. Then, we found that TSPAN7 deletion interrupted the integrin β1/FAK/SRC signal pathway that was followed by the down-regulation of PSD95, SYN, and GluR1/2, which are key synaptic integrity-related proteins. Furthermore, reactivation of SRC restored the expression of synaptic integrity-related proteins in primary neurons of TSPAN7 knockout brains. Taken together, our results suggested that TSPAN7 knockout caused ASD-like and ID-like behaviors in rats and impaired neuronal synapses possibly through the down-regulation of the integrin β1/FAK/SRC signal pathway, which might be a new mechanism on regulation of synaptic proteins expression and on ASD pathogenesis by mutated TSPAN7. These findings provide novel insights into the role of TSPAN7 in psychiatric diseases and highlight integrin β1/FAK/SRC as a potential target for ASD therapy.