Autism spectrum disorder (ASD) and Rett Syndrome (RTT) are neurodevelopmental disorders associated with early life behavioural impairments. Despite differences in etiology, both disorders are associated with an alteration in brain maturation, a developmental event thought to have permanent consequences. Recent studies have reversed the cellular and behavioural impairments in mouse models of RTT. However, it is unknown how these interventions ameliorate the cellular maturation impairments across the brain and over time, important information needed for assessing treatment efficacy. Magnetic Resonance Imaging (MRI) is an imaging modality that has the ability to longitudinally acquire high-resolution neuroanatomical information from the mouse brain. In this project, the Mecp2 mouse model of RTT will be tracked longitudinally with MRI over the time course of treatment with three interventions: a) full rescue of the Mecp2 gene, which restores neuronal activity and behaviour b) enriched housing, a condition that stimulates neuronal growth and c) treatment with a novel candidate pharmaceutical (NNZ-2566, Neuren) thought to restore the neuronal homeostasis. The efficacy of the enriched environment and NNZ-2566 will be verified by comparing the reversal dynamics with the genetic rescue of Mecp2. Therefore, these studies will compare and test the effectiveness of different interventions to reduce the core and associated phenotypes shared between Rett syndrome and ASD.
Interagency Autism Coordinating Committee (IACC)
Autism Research Database (AFD)
