Journal
NEUROSCIENCE LETTERS
Volume 764, Issue -, Pages -Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.neulet.2021.136241
Keywords
Vorinostat; SAHA; Histone deacetylase inhibitor; ASH1L; Autism spectrum disorder; Intellectual disability
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Funding
- National Institutes of Health [R01GM127431]
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This study demonstrated that loss of ASH1L in mice can cause developmental defects and autistic-like behaviors, and treatment with vorinostat significantly improved these deficits.
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.
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