Assessment of Glutamatergic Neurosystem in Fragile X Syndrome for Targeted Therapy
[Technical Report, Annual Report]
MASSACHUSETTS GENERAL HOSPITAL BOSTON
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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 inhibitor enhance glutamate induced signaling. DTI and MEG will be used to examine disruptions in structural and functional brain connectivity. The longitudinal follow up studies showed group differences of mGluR5 expression, learning, memory, and general motor performance behaviors in the mice as a function of gender and diagnostic groups, paving a way for examining therapeutic response on mGluR5 expression and associated behavioral changes during progression of disease. For human studies we have set-up working protocols for neuroimaging, acclimation, and clinical testing, and completed data collectionPET, MRI, DTI and MEG with nine control and FXS subjects. In the human data, uptake of 18FFPEB showed regional correspondences with those seen in mouse data providing an outstanding translational aspect to investigate FXS related bio-behavior and develop therapeutic approaches.
- Medicine and Medical Research