Vorinostat, a histone deacetylase inhibitor, ameliorates the sociability and cognitive memory in an Ash1L-deletion-induced ASD/ID mouse model

•Postnatal administration of vorinostat (SAHA) ameliorates the core ASD-like behaviors in the Ash1L-deletion-induced ASD/ID mouse model.•Postnatal administration of vorinostat (SAHA) ameliorates the cognitive memory in the Ash1L-deletion-induced ASD/ID mouse model.•Different behavioral deficits have distinct responses to vorinostat (SAHA) treatment.•No obvious drug toxicity was observed during low-dose vorinostat (SAHA) treatment. Autism spectrum disorder (ASD) and intellectual disability (ID) are neurodevelopmental diseases associated with various gene mutations. Previous genetic and clinical studies reported that ASH1L is a high ASD risk gene identified in human patients. Our recent study used a mouse model to demonstrate that loss of ASH1L in the developing mouse brain was sufficient to cause multiple developmental defects, core autistic-like behaviors, and impaired cognitive memory, suggesting that the disruptive ASH1L mutations are the causative drivers leading the human ASD/ID genesis. Using this Ash1L-deletion-induced ASD/ID mouse model, here we showed that postnatal administration of vorinostat (SAHA), a histone deacetylase inhibitor (HDACi), significantly ameliorated both ASD-like behaviors and ID-like cognitive memory deficit. Thus, our study demonstrates that SAHA is a promising reagent for the pharmacological treatment of core ASD/ID behavioral and memory deficits caused by disruptive ASH1L mutations.