Description

Fetal alcohol spectrum disorders (FASD) is an umbrella term used to describe cognitive and behavioral alterations caused by prenatal alcohol exposure. Caretakers often report that children with FASD experience sleep problems. Unfortunately, interventions to improve sleep have not been well studied. Interestingly, supplementation with the essential nutrient choline can mitigate behavioral alterations that are present after prenatal alcohol exposure, such as hyperactivity and spatial learning deficits. Choline is a precursor to acetylcholine, a neurochemical that is also involved with sleep-wake modulation. However, it is unknown whether choline supplementation can improve sleep alterations associated with FASD. Therefore, the present study investigated the effects of developmental alcohol exposure and choline supplementation on sleep using an animal model. 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 received subcutaneous injections with choline chloride (100 mg/kg/day) or saline from PD 10-30. Thus, this study included a 2 (ethanol or sham control) x 2 (choline or saline) x 2 (male, female) design. 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 and sleep bout length, during the light and dark cycles were recorded. Subjects that were exposed to ethanol during development slept less during the dark cycle, an effect seen in both sexes, but more robust in males. Moreover, developmental alcohol exposure led to more variability in sleep bout duration. Importantly, choline supplementation mitigated the effects of ethanol on sleep, producing sleep durations that did not differ from that of controls. Choline specifically increased sleep bout duration in ethanol-exposed subjects, suggesting that choline can modify sleep patterns. These results illustrate that alcohol exposure during late gestation can cause sleep disturbances and suggests that postnatal choline supplementation may alleviate sleep problems associated with developmental alcohol exposure. Importantly, this nutritional intervention was administered after the alcohol insult, suggesting that nutritional supplements in children with FASD may improve sleep quality. Supported by AA012446 and T32AA013525.