The effects of dietary supplementation with n-3 fatty acids on the behavioral and neuroinflammatory phenotype of the Fmr1 knockout mouse

Abstract

Fragile X Syndrome (FXS) is a neurodevelopmental disorder caused by a genetic trinucleotide (CGG) overexpansion mutation in the FMR1 gene coding for fragile X mental retardation protein (FMRP). This disorder is characterized by marked intellectual disability, as well as other autistic-like behavioral phenotypes. Supplementation with omega-3 polyunsaturated fatty acids (n-3 PUFAs) has been proposed as an alternative treatment for a variety of neurodevelopmental disorders, including Autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD). Previous results have examined the efficacy of this treatment paradigm in the FXS mouse model, though it is not known how the efficacy varies between background strains. In the present study, male FVB/129 Fmr1 knockout and Fmr1 wildtype littermates were assigned to one of three diet conditions following weaning on PD21: standard lab chow, EPA/DHA enriched chow, and a diet controlling for the increase in fat associated with the former. Upon reaching postnatal day 90, animals were tested in a several behavioral assays, which included elevated plus maze, social partition, nose poke assay, delay fear conditioning and prepulse inhibition. Results revealed that supplementation with omega-3 fatty acids attenuated alterations in prepulse inhibition behavior and hyperactivity. Results also revealed that the increased dietary fatty acid composition significantly impacted sociability and repetitive behavior. These behavioral changes were associated with reduction in hippocampal expression of IL-6 resulting from dietary supplementation omega-3 fatty acids.