Postnatal choline supplementation improves sleep in a rat model of developmental alcohol exposure.

BACKGROUND: Fetal alcohol spectrum disorders (FASD) is an umbrella term used to describe physical, neuropathological, and behavioral alterations caused by prenatal alcohol exposure. Caretakers often report that children with FASD experience sleep problems. However, interventions to improve sleep have not been well-studied in this population. Interestingly, supplementation with the essential nutrient choline can attenuate many behavioral alterations associated with prenatal alcohol exposure. Moreover, choline is a precursor to acetylcholine, a neurochemical that is also involved in sleep-wake modulation. Using an animal model, this study investigated the effects of developmental alcohol exposure on sleep and examined whether postnatal choline supplementation can modulate sleep alterations associated with FASD. METHODS: Sprague-Dawley rat pups received ethanol (5.25 g/kg/day, 11.9% v/v) or sham intubations from postnatal days (PD) 4-9, a period of development equivalent to the human third-trimester brain growth spurt. Subjects then received subcutaneous injections with choline chloride (100 mg/kg/day) or saline from PD 10-30. On PD 32-37, subjects were individually housed to measure sleep-wake behaviors using the PiezoSleep Adapt-A-Base System. Sleep parameters, including sleep time, bout length, and number, were recorded. RESULTS: Ethanol-exposed subjects, particularly females, slept less during the dark cycle. In addition, females exposed to developmental alcohol exhibited more night-to-night variability in sleep duration, consistent with findings from clinical populations. In contrast, choline supplementation increased sleep duration, particularly among males exposed to developmental alcohol. Choline specifically increased sleep bout duration in ethanol-exposed subjects during the dark cycle, suggesting that choline can modify sleep patterns among subjects exposed to prenatal alcohol. CONCLUSIONS: These results illustrate that alcohol exposure during late gestation may lead to sleep disturbances and suggest that postnatal choline supplementation affects sleep quality. Importantly, this nutritional intervention was administered after the alcohol insult, suggesting that nutritional supplements in children with FASD may impact sleep problems.