Food and Behaviour Research

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Rescue of ethanol-induced FASD-like phenotypes via prenatal co-administration of choline

Bottom RT, Abbott CW 3rd, Huffman KJ. (2020) Neuropharmacology 168 107990. doi: 10.1016/j.neuropharm.2020.107990. May 15; Epub 2020 Feb 7. 

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Abstract:

Maternal consumption of alcohol during pregnancy can generate a multitude of deficits in the offspring. Fetal Alcohol Spectrum Disorders, or FASD, describe a palette of potentially life-long phenotypes that result from exposure to ethanol during human gestation. There is no cure for FASD and cognitive-behavioral therapies typically have low success rates, especially in severe cases. The neocortex, responsible for complex cognitive and behavioral function, is altered by prenatal ethanol exposure (PrEE).

Supplementation with choline, an essential nutrient, during the prenatal ethanol insult has been associated with a reduction of negative outcomes associated with PrEE. However, choline's ability to prevent deficits within the developing neocortex, as well as the underlying mechanisms, remain unclear.

Here, we exposed pregnant mice to 25% ethanol in addition to a 642 mg/L choline chloride supplement throughout gestation to determine the impact of choline supplementation on neocortical and behavioral development in ethanol-exposed offspring.

We found that concurrent choline supplementation prevented gross developmental abnormalities associated with PrEE including reduced body weight, brain weight, and cortical length as well as partially ameliorated PrEE-induced abnormalities in intraneocortical circuitry. Additionally, choline supplementation prevented altered expression of RZRβ and Id2, two genes implicated in postmitotic patterning of neocortex, and global DNA hypomethylation within developing neocortex.

Lastly, choline supplementation prevented sensorimotor behavioral dysfunction and partially ameliorated increased anxiety-like behavior observed in PrEE mice, as assessed by the Suok and Ledge tests.

Our results suggest that choline supplementation may represent a potent preventative measure for the adverse outcomes associated with PrEE.

FAB RESEARCH COMMENT:

Most so-called 'fetal alcohol spectrum disorders' (FASD) are likely to go undetected, unless maternal alcohol consumption is extreme enough to be on record. However, the resulting early brain damage is irreversible, and can lead to difficulties with sensory processing, mood, behaviour and learning.  FASD can be a factor in numerous descriptive diagnoses, including ADHD, dyspraxia or other childhood neurodevelopmental disorders; anxiety disorders; general learning disabilities, or serious mental health problems such as schizophrenia.

This animal study shows that many of the damaging effects of prenatal alcohol on brain development can be alleviated by dietary supplementation of mothers during pregnancy with choline - a B-vitamin like substance important for methylation (and thus gene expression and regulation) as well as a key component of brain and nerve cell membranes.

Despite public health advice, alcohol consumption in pregnancy remains all too common. These findings have such important potential implications for public health that human clinical studies are urgently warranted.

Meanwhile - as choline is 
relatively lacking from the diets of most women during pregnancy (and is not included in many prenatal vitamin supplements), raising awareness of the importance of this key nutrient in mothers-to-be and the health professionals who care for them is already overdue, as human studies show that higher prenatal choline status in mothers-to-be also protects against the neurodevelopmental problems in children that often follow from viral infections in prenancy.