The Role of the New mTOR Complex, MTORC2, in Autism Spectrum Disorders
Abstract
The goal of my DOD-supported research is determine the role of the new mTOR complex (mTORC2) in Autism Spectrum Disorder (ASD). ASD individuals exhibit impaired social interactions, seizures and abnormal repetitive behavior. In addition, 70-80% of autistic individuals suffer from mental retardation. Autism is a heritable genetically heterogeneous disorder and mutations in negative regulators of the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway, such as PTEN were associated with ASD. Here, we show that in the hippocampus of Pten fb-KO mice where Pten is conditionally deleted in the murine forebrain the activity of both mTORC1 and mTORC2 is increased. In addition, Pten fb-KO mice exhibit seizures, learning and memory and social deficits. Our remarkable preliminary data show that genetic inhibition of mTORC2 activity in Pten-deficient mice significantly promotes survival. In addition, Pten-rictor fb- double KO (DKO) mice, in which mTORC2 activity is restored to normal levels, EEG seizures, learning and memory as well as social phenotypes, are all rescued. In the second year, we will study the molecular mechanism underlying this process. These insights hold the promise for new treatment of ASD.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2014
- Accession Number
- ADA613836
Entities
People
- Mauro Costa-Mattioli
Organizations
- Baylor College of Medicine