Assessment Of Glutamatergic Neurosystem In Fragile X Syndrome For Targeted Therapy
Abstract
The purpose of the proposed research is to examine the role of mGluR5 expression in the brain in relation to behavioral symptoms including anxiety, learning, memory and locomotor activity in adults with Fragile X syndrome and genetically-modified mice (FMR1 Knock Out) towards developing an improved neurobiological model of the disorder. To this end, the study will also evaluate the outcomes of therapeutic drugs in FMR1 Knock Out mice targeting mGluR5 to inhibit or enhance glutamate induced signaling. DTI and MEG will be used examine disruptions in structural and functional brain connectivity. Preliminary findings show no group differences of mGluR5 expression or in learning, memory, or general motor performance behaviors in the mice as a function of gender or diagnostic group, paving the way for examining modulations inmGluR5 expression and associated behavioral changes with gender or progression of disease. For human studies we have set-up working protocols for neuroimaging, acclimation, and clinical testing, and completed data collection (PET, MRI, DT Iand MEG) with two control subjects. Three patients with Fragile X have been also been scheduled. In the human data, uptake of [18F]FPEB shows regional correspondences with those seen in mouse data and is consistent with the existing literature.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2018
- Accession Number
- AD1055813
Entities
People
- Anna-Liisa Brownell
- Maria Mody
Organizations
- Massachusetts General Hospital