High Maternal Choline Consumption During Pregnancy and Nursing Alleviates Deficits in Social Interaction and Improves Anxiety‐like Behaviors in the BTBR T+Itpr3tf /J Mouse Model of Autism

Abstract

Autism is a neurodevelopmental disorder with multiple genetic and environmental risk factors. Choline is an essential nutrient for brain development and high choline intake during prenatal and/or early postnatal periods is neuroprotective. We examined the effects of perinatal choline supplementation on anxiety, social and repetitive behaviors in the BTBR T+Itpr3tf/J (BTBR) mouse model of autism. The BTBR or the control C57BL/6J (B6) females were fed a control or high‐choline diet throughout pregnancy and lactation. After weaning to a control diet, juvenile and adult offspring were evaluated using open field (OF), elevated plus maze (EPM), marble burying, and three‐chamber social interaction tests. As expected, control‐diet BTBR mice had higher OF locomotor activity, impaired social preference, and increased marble burying compared to control‐diet B6 mice. Choline supplementation decreased digging behavior and elevated the percentage of entries and time spent in open arms in the EPM by BTBR mice without effects on locomotion. Choline supplementation remarkably improved impairments in social interaction in BTBR mice at both ages and had no effect in B6 mice. We note that the behavioral‐phenotype‐related genetic quantitative trait loci in BTBR mice contain genes associated with the biochemistry of choline: Chrna3, Chrna5, Chrnb4, Pcyt1b, Chpt1, Pld1, Ppap2c, Mthfd1, Mthfs, Slc19a1, Dnmt3l, Mecp2. In conclusion, high choline intake during early development can prevent or reduce deficits in social behavior and anxiety in an autistic mouse model, revealing a strategy for the treatment/prevention of autism spectrum disorders.