Grant: Operating Grant

Rett syndrome and Fragile-X mental retardation are debilitating neurodevelopmental disorders that strike young infants after apparently many months of normal growth and development. Although there is currently no effective medication, the time delay suggests a "window of opportunity" for therapeutic intervention may exist. Each disorder presents with a spectrum of symptoms, however, afflicted children commonly possess autistic features. This finding has suggested to some that Rett syndrome and Fragile-X mental retardation may have a common molecular basis. In this grant application, we provide evidence for a novel signaling pathway triggered in early brain development by the neurotransmitter, L-glutamate. Importantly, this pathway is absent in a mouse model of Fragile-X mental retardation. We hypothesize it is also deficient in Rett syndrome. Experiments are planned to study the properties of this signaling pathway with the aim of rescuing its expression. Our work demonstrates for the first time a missing molecular event in the brains of Fragile-X sufferers that may also be lacking in Rett syndrome. The benefit of this work is that it may provide a basis for the development of clinically relevant compounds to treat these disorders early on in childhood.