Maternal Choline Supplementation Is Associated with Lasting Improvements in Behavioral Effects of Prenatal Alcohol Exposure in the C57BL/6J Mouse

Background. Prenatal alcohol exposure (PAE) causes changes in growth, metabolic outcomes, and behavior that can last into adulthood. Treatment with choline has proven efficacious in the short term in animal models and improves some outcomes in people with Fetal Alcohol Spectrum Disorder. Here we tested the hypothesis that maternal supplementation with choline would mitigate behavioral effects of PAE through adulthood. Methods. Pregnant C57BL/6J mice were given alcohol (ALC; 3 g/kg body weight) and choline (Cho; 100 mg/kg) once per day from embryonic day (E) 8.5 through E17.5. Control mice received isocaloric maltodextrin via gavage. Animals that did not receive choline were handled but not injected. Male and female offspring were weighed and tested at 2 months of age (2 mo), 6 mo, 12 mo, and 18 mo on the open field, accelerating rotarod, and fear conditioning tests. Results. Body weight increased with age; however, ALC mice had greater body weight than age-matched controls (CON), and Cho decreased body weight in both CON and ALC mice. Both CON and ALC mice performed better on motor behaviors (open field and rotarod) at younger ages and better on fear conditioning in mid-adulthood (6 and 12 mo). CON mice typically outperformed same-age, same-sex ALC mice, and ALC-Cho mice performed better than ALC mice on fear conditioning but not on motor outcomes. Conclusions. Our data suggest that maternal choline supplementation can modulate body weight increase through later adulthood in both CON and ALC offspring and also confers lasting behavioral benefits in the context of PAE. The similar age-related trends in behavior for both groups suggest that PAE did not accelerate the behavioral decline.