This project explores the untested hypothesis that the soy phytoestrogen daidzein exacerbates fragile X syndrome (FXS) phenotypes. FXS is the most common form of inherited intellectual disability. Serendipitous findings from our laboratory indicate that a soy-based diet increases seizure incidence in a mouse model of FXS, Fmr1KO mice, as well as in infants later diagnosed with autism. In the mouse studies, a seizure-promoting ingredient in the soy was identified as the soy phytoestrogen daidzein. We hypothesize that a soy-based diet during postnatal development exacerbates multiple FXS phenotypes. This grant application is a pilot study to determine the pharmacokinetics of daidzein and its metabolites in WT and Fmr1KO mice as well as their effects on well-established FXS phenotypes including seizure threshold, anxiety, hyperactivity and sensorimotor gating. Successful experimental outcomes will provide the preliminary data for an RO1 grant application to test the rescue of additional FXS phenotypes in Fmr1KO mice in response to a soy-free diet as well as the underlying molecular mechanism. The long-term goal of this project is provide solid pre-clinical data in Fmr1KO mice that support the restriction of soy-based infant formulas for babies with FXS and other neurodevelopmental disorders.
The goal of this project is to determine if a soy-rich diet exacerbates Fragile X phenotypes. This proposal specifically assesses the efficacy of soy, and the soy phytoestrogen daidzein, on audiogenic seizures, anxiety, pre-pulse inhibition and biomarker levels in Fmr1KO mice, a rodent model for Fragile X. There is a currently a dearth of therapeutics for the treatment of Fragile X and successful outcomes from these experiments would justify the use of soy-free infant formulas for babies with Fragile X
|Westmark, C J; Sokol, D K; Maloney, B et al. (2016) Novel roles of amyloid-beta precursor protein metabolites in fragile X syndrome and autism. Mol Psychiatry 21:1333-41|
|Westmark, Cara J (2014) The quest for fragile X biomarkers. Mol Cell Pediatr 1:1|
|Westmark, Cara J (2013) Soy Infant Formula may be Associated with Autistic Behaviors. Autism Open Access 3:|