title: 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.
authors: Department of Biochemistry and Goodman Cancer Research Centre; McGill University; Montreal, QC Canada.
authors: Christos G
authors: CG
authors: Gkogkas
authors: Department of Biochemistry and Goodman Cancer Research Centre; McGill University; Montreal, QC Canada.
authors: Nahum
authors: N
authors: Sonenberg
keywords: ASD; autism-like behaviors; excitation-inhibition balance; mouse models; translational control