Choline and Working Memory Training Improve Cognitive Deficits Caused by Prenatal Exposure to Ethanol.

Jaylyn Waddell,Sandra Mooney

doi:10.3390/nu9101080

Abstract

Prenatal ethanol exposure is associated with deficits in executive function such as working memory, reversal learning and attentional set shifting in humans and animals. These behaviors are dependent on normal structure and function in cholinergic brain regions. Supplementation with choline can improve many behaviors in rodent models of fetal alcohol spectrum disorders and also improves working memory function in normal rats. We tested the hypothesis that supplementation with choline in the postnatal period will improve working memory during adolescence in normal and ethanol-exposed animals, and that working memory engagement during adolescence will transfer to other cognitive domains and have lasting effects on executive function in adulthood. Male and female offspring of rats fed an ethanol-containing liquid diet (ET; 3% v/v) or control dams given a non-ethanol liquid diet (CT) were injected with choline (Cho; 100 mg/kg) or saline (Sal) once per day from postnatal day (P) 16–P30. Animals were trained/tested on a working memory test in adolescence and then underwent attentional set shifting and reversal learning in young adulthood. In adolescence, ET rats required more training to reach criterion than CT-Sal. Choline improved working memory performance for both CT and ET animals. In young adulthood, ET animals also performed poorly on the set shifting and reversal tasks. Deficits were more robust in ET male rats than female ET rats, but Cho improved performance in both sexes. ET male rats given a combination of Cho and working memory training in adolescence required significantly fewer trials to achieve criterion than any other ET group, suggesting that early interventions can cause a persistent improvement.

Highlights

Fetal alcohol spectrum disorder (FASD) is an umbrella term used to describe the range of disabilities caused by prenatal alcohol exposure
Mild prenatal ethanol exposure resulted in long term cognitive deficits in rats that were typically more apparent in males than females
Intervention during adolescence in the form of nutritional supplementation with choline and training on a working memory task was effective in males, and the combination was more effective than either intervention alone

Summary

Introduction

Fetal alcohol spectrum disorder (FASD) is an umbrella term used to describe the range of disabilities caused by prenatal alcohol exposure. Children and adults with FASD perform poorly in many tasks that assess executive function [3,4,5,6,7,8,9]. The term executive function describes efficient interaction between many cognitive domains, such as allocation of attention, impulse control or response inhibition, mental flexibility and working memory [10,11]. Successful engagement of these domains supports the ability to keep information ‘in mind’, attend to appropriate cues and update information as contingencies change. Though many studies have documented deficits in executive function evident in FASD, few studies have attempted to improve these deficits with cognitive domain-specific training despite positive outcomes [12,13]

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Conclusion