INVESTIGATING THE ROLE OF CHOLINE AS A NUTRACEUTICAL FOR RETT SYNDROME

Abstract

Rett syndrome (RTT) is a postnatal neurodevelopmental disorder, with 95% of RTT cases resulting from mutations in the methyl-CpG-binding protein 2 (MECP2) gene. Choline, a dietary micronutrient, has been reported to enhance motoric function in RTT mouse models. However, its exact mechanism of action is unknown. In this study, postnatal choline treatment to Mecp2-conditional knockout mice improved their behavioural deficits. RTT neuronal morphology in vivo and in vitro was shown to be rescued by choline. Through the use of specific inhibitors, synthesis of phosphatidylcholine from choline was found to be essential in mediating the neuronal improvements. Further, differences were observed in the lipid metabolite profiles of choline-supplemented patient-specific induced pluripotent stem cell-derived neurons with different MECP2 mutations. Taken together, these data reveal a role of choline in modulating neuronal plasticity and lipid signalling, possibly leading to behavioural improvement, and hence, a potential for using choline to treat RTT.