Translational control and autism-like behaviors

Abstract

AUTISM SPECTRUM DISORDERS (ASD) CONSIST OF A SPECTRUM OF NEURODEVELOPMENTAL DISEASES WITH THREE SALIENT FEATURES: reduced social interactions, impaired communication and repetitive/stereotyped behaviors. In a recent study we found that increased eIF4E (eukaryotic initiation factor 4E)-dependent protein synthesis as a result of genetic deletion of Eif4ebp2 (eIF4E-binding protein 2) in mice, stimulates the production of neuroligins (Nlgns, synaptic cell-adhesion molecules important for synapse regulation) and engenders an imbalance of excitatory to inhibitory synaptic transmission (E/I) in CA1 pyramidal neurons. This imbalance is accompanied with deficits in social interaction, communication and repetitive/stereotyped behaviors in Eif4ebp2-/- mice. Using a compound that blocks cap-dependent translation or by knocking down Nlgn1, we restored the E/I balance and reversed the autism-like social deficits.