Suppression of Akt-mTOR pathway rescued the social behavior in Cntnap2-deficient mice
Abstract
Autism spectrum disorders (ASD) form a heterogeneous, neurodevelopmental syndrome characterized by deficits in social interactions and repetitive behavior/restricted interests. Dysregulation of mTOR signaling has been implicated in the pathogenesis of certain types of ASD, and inhibition of mTOR by rapamycin has been demonstrated to be an effective therapeutics for impaired social interaction in Tsc1+/-, Tsc2+/-, Pten-/- mice and valproic acid-induced ASD animal models. However, it is still unknown if dysregulation of mTOR signaling is responsible for the ASD-related deficit caused by other genes mutations. Contactin associated protein-like 2 (CNTNAP2) is the first widely replicated autism-predisposition gene. Mice deficient in Cntnap2 (Cntnap2-/- mice) show core ASD-like phenotypes, and have been demonstrated as a validated model for ASD-relevant drug discovery. In this study, we found hyperactive Akt-mTOR signaling in the hippocampus of Cntnap2-/- mice with RNA sequencing followed with biochemical analysis. Treatment with Akt inhibitor LY294002 or mTOR inhibitor rapamycin rescued the social deficit, but had no effect on hyperactivity and repetitive behavior/restricted behavior in Cntnap2-/- mice. We further showed that the ef...Continue Reading
References
Linkage, association, and gene-expression analyses identify CNTNAP2 as an autism-susceptibility gene
Neuroligin-3-deficient mice: model of a monogenic heritable form of autism with an olfactory deficit
Citations
Methods Mentioned
Software Mentioned
Related Concepts
Related Feeds
Attention Disorders
Attention is involved in all cognitive activities, and attention disorders are reported in patients with various neurological diseases. Here are the latest discoveries pertaining to attention disorders.
Autism
Autism spectrum disorder is associated with challenges with social skills, repetitive behaviors, and often accompanied by sensory sensitivities and medical issues. Here is the latest research on autism.