An Epigenetic Approach to Autism

Mice deficient in the Shank3 gene, which encodes a scaffolding protein in glutaminergic N-methyl-d-aspartate receptors (NMDARs), exhibit autism-like behaviors (e.g., repetitive behaviors and social preference deficits). In a preclinical study, researchers examined whether manipulations of expression of this gene could improve these behaviors.

Compared with wild-type mice, Shank3-deficient mice had lower histone H3 acetylation in the prefrontal cortex. In Shank3-deficient mice, but not wild-type mice, the histone deacetylase (HDAC) inhibitor romidepsin increased H3 acetylation, social exploration, and interactions; behavioral effects in young mice lasted 3 weeks after a single dose. Knockdown of the HDAC2 gene improved social deficits. Severa…