Choline supplementation following third-trimester-equivalent alcohol exposure attenuates behavioral alterations in rats.

Abstract

Despite the known adverse consequences of prenatal alcohol exposure, some pregnant women continue to drink alcohol, making it imperative to identify treatments for children with fetal alcohol spectrum disorders. The authors recently reported that perinatal choline supplementation can reduce some fetal alcohol effects (J. D. Thomas, M. Garrison, & T. M. O'Neill, 2004), and the present study examined whether choline supplementation is effective when administered after third-trimester-equivalent ethanol treatment. Rat pups were exposed to 6.0 g/kg/day ethanol during the neonatal brain growth spurt (Postnatal Days [PD] 4-9) and treated with choline chloride (0, 10, 50, or 100 mg/kg) from PD 10-30. Behavioral testing occurred after choline treatment had ceased. Female subjects exposed to ethanol were overactive and exhibited spatial learning deficits, effects that were attenuated with all doses of choline supplementation. These data indicate that choline supplementation can alter brain development following a developmental insult. Moreover, the data suggest that early dietary interventions may reduce the severity of some fetal alcohol effects, even when administered after birth.

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).…”

Prenatal choline supplementation attenuates neuropathological response to status epilepticus in the adult rat hippocampus

“…While this study examined only the neuroprotective effects of prenatal choline supplementation, some reported neuroprotective actions of choline appear to be postnatal (Thomas et al, 2007); thus, infants at risk for seizures might benefit from added choline to formula or choline supplementation to mother's diet. These data also suggest that prenatal choline deficiency may make offspring more vulnerable to the deleterious consequences of seizures, though this remains to be determined.…”

“…Prenatal and early postnatal choline supplementation has also been shown to protect against impairments in performance on hippocampal-dependent tasks caused by aging (Meck et al, 1988(Meck et al, , 1989Meck & Williams, 2003;McCann et al, 2006) or neonatal alcohol exposure (Thomas et al, 2004(Thomas et al, , 2007Wagner & Hunt, 2006). While the mechanism by which prenatal choline supplementation confers neuroprotection is not fully understood, choline is a vital nutrient important for several biological functions: acetylcholine synthesis, building biological membranes, cell signaling, and methyl donation (Blusztajn, 1998;Zeisel, 2004Zeisel, , 2006.…”

Prenatal choline supplementation increases sensitivity to time by reducing non-scalar sources of variance in adult temporal processing

“…In terms of neuroplasticity, adult hippocampal slices from prenatally choline supplemented rats exhibit a lower threshold for the induction of long-term potentiation compared with slices from control rats (Jones et al, 1999;Pyapali et al, 1998). Furthermore, perinatal choline supplementation can alter behavior and neurochemistry following a variety of developmental disorders, including the alleviation of behavioral abnormalities associated with fetal alcohol syndrome in Sprague-Dawley rats (Thomas et al, 2000(Thomas et al, , 2004(Thomas et al, , 2007Wagner and Hunt, 2006), attenuation of some of the motor deficits observed in a Mecp21 lox mouse model of Rett syndrome (Nag and Berger-Sweeney, 2007), and the improvement of sensory gating in a DBA/2 mouse model of schizophrenia that exhibits reduced numbers of hippocampal α7 nicotinic receptors (Stevens et al, 2007). Consequently, it was of interest in the present study to investigate the effects of prenatal choline supplementation on the implementation of S1 and S2 response thresholds involved in duration discrimination tasks such as the PI procedure due to the potential sensorimotor enhancing actions of α7 nicotinic receptor agonists during early development (Meyer et al, 1998).…”