Prenatal choline supplementation mitigates behavioral alterations associated with prenatal alcohol exposure in rats

Abstract

BACKGROUND Prenatal alcohol exposure can alter physical and behavioral development, leading to a range of fetal alcohol spectrum disorders (FASD). Despite warning labels, pregnant women continue to drink alcohol, creating a need to identify effective interventions to reduce the severity of alcohol’s teratogenic effects. Choline is an essential nutrient that influences brain and behavioral development. Recent studies indicate that choline supplementation can reduce the teratogenic effects of developmental alcohol exposure. The present study examined whether choline supplementation during prenatal ethanol treatment could mitigate the adverse effects of ethanol on behavioral development. METHODS Pregnant Sprague-Dawley rats were intubated with 6 g/kg/day ethanol in a binge-like manner from gestational days 5–20; pair-fed and ad lib chow controls were included. During treatment, subjects from each group were intubated with either 250 mg/kg/day choline chloride or vehicle. Spontaneous alternation, parallel bar motor coordination, Morris water maze, and spatial working memory were assessed in male and female offspring. RESULTS Subjects prenatally exposed to alcohol exhibited delayed development of spontaneous alternation behavior and deficits on the working memory version of the Morris water maze during adulthood, effects that were mitigated with prenatal choline supplementation. Neither alcohol nor choline influenced performance on the motor coordination task. CONCLUSIONS These data indicate that choline supplementation during prenatal alcohol exposure may reduce the severity of fetal alcohol effects, particularly on alterations in tasks that require behavioral flexibility. These findings have important implications for children of women who drink alcohol during pregnancy.

Randomized, double-blind, placebo-controlled clinical trial of choline supplementation in school-aged children with fetal alcohol spectrum disorders

“…An examination of the groups separately revealed that small effect sizes and sample sizes would have to have been inordinately large to confidently draw conclusions from the results; in addition, the possibility of a type II error could not be ruled out (achieved power ranged from 0.13 to 0.84). The null findings of this clinical trial were unanticipated because of the strong evidence that has suggested beneficial effects of choline supplementation in animal models of both typical development (39) and prenatal alcohol exposure (3)(4)(5)(6)(7)(8)10). However, this investigation was only one of a few trials to translate the aforementioned animal research to a human clinical trial of choline supplementation in FASDs, and previous studies, at earlier ages, have suggested some positive beneficial effects (13,14).…”

“…Notably, our group was the first, to our knowledge, to examine the effects of a nutritional intervention of choline with the use of a rodent model of FASDs (3). Through a series of studies, we showed that choline reduces the severity of alcohol's adverse effects on behavioral development whether administered perinatally (4,5) or postnatally after alcohol exposure has occurred (3,6,7). Choline mitigates behavioral deficits on tasks that depend on the functional integrity of the hippocampus and prefrontal cortex including spatial learning and memory (8), hyperactivity (8), trace classical conditioning (9,10), and working memory (3).…”

The Impact of Traditional Food and Lifestyle Behavior on Epigenetic Burden of Chronic Disease

“…Increased miR-467b-5p in Slc17a6 promoter resulting in hypomethylation of hippocampal H3K4me3 at the Slc17a6 promoter, with corresponding increased mRNA levels of hippocampal Slc17a6, although its protein product VGLUT2 was decreased Rat Maternal ethanol exposure during pregnancy [110,112,114,128,[268][269][270][271] Behavioral, learning and memory deficits, and decreased birth and brain weights, and incisor emergence [284] Hypomethylation of the sperm LINE-1 gene Human/ cohort study Maternal exposure to organophosphate pesticides and persistent organic pollutants [291] Decreased adiponectin levels with increasing levels of cord blood p,p′-dichlorodiphenyl dichloroethene (DDE) in female offsprings…”

“…) [110,112,114,128] Choline supplementation enhanced offsprings' ethanol induced learning and memory deficits…”

“…[264] Prenatal exposure to alcohol is demonstrated to induce extensive DNA methylation changes in human [265][266][267] and rodent offsprings ( Table 2). [110,112,114,120,128,[268][269][270][271][272] These effects are possibly transmitted via methylation of the paternal germ line, [273] although alcohol-induced placental epigenetic changes suggest the involvement of the female germ line. [264] The rising harmful use of alcohol, [274] just as tobacco use, [275] imposes a huge public health burden, and may have contributed in shaping the history of some NCCDs in recent years.…”