Prenatal Choline Intake Increases Gray and White Matter: Piglet Study

Summary: Researchers report piglets of mothers who were fed a choline rich diet had increased white and gray matter in the brain.

Source: University of Illinois.

Choline intake during pregnancy can influence infant metabolism and brain development, according to a series of studies from the University of Illinois. Although the role of choline in neurodevelopment has been studied before in rodents, the new research, done with pigs, has more relevance to humans.

“We know the pig is a good model for humans because they have the same nutrient requirements, similar metabolic function, and also have very similar brain development, following the same growth trajectories,” explains Austin Mudd, a doctoral student in the Neuroscience Program at U of I. “The pig is bridging the gap between the mechanistic work we see in rodents and that higher-level cognitive function that they’re looking at in humans.”

Choline, found in liver, eggs, wheat germ, and other foods, is an essential nutrient in human and animal diets. It’s required to make cell membranes, neurotransmitters, and myelin, the fatty sheath surrounding nerve cells. But most adults, including pregnant women, don’t consume enough.

“In the U.S., 90 percent of us don’t meet our choline requirement,” Mudd says. “And the most recent data says pregnant women, who should consume 450 milligrams per day, may not even be reaching 300 milligrams.”

To understand how choline deficiency affects the developing brain during and after pregnancy, Mudd and his collaborators gave pregnant sows choline-deficient or choline-sufficient diets through the second half of their pregnancies. After weaning, piglets were fed choline-deficient or choline-sufficient milk replacer for 30 days. Then the month-old piglets were scanned by magnetic resonance imaging (MRI).

Mudd analyzed images of the piglet brains in terms of volume and makeup. The first analysis, reported in a 2016 article in Nutritional Neuroscience, compared the volumes of 19 brain regions in piglets that had received deficient or sufficient choline prenatally and postnatally. The second analysis, published last week in Current Developments in Nutrition, corrected for volume differences to isolate differences in grey and white matter concentration in the piglets’ brains.

“In pigs from choline-deficient moms, their brains were about 10 percent smaller overall,” Mudd says. And 11 of the 19 regions were significantly smaller in choline-deficient brains.

When Mudd corrected for these volume differences to look specifically at grey and white matter concentration, the story was the same. Piglets whose mothers consumed sufficient choline during pregnancy had higher concentrations of grey and white matter in the brain’s cortical regions.

Grey matter is primarily made up of the neurons themselves, while white matter comprises the material that connects neurons and bridges different parts of the brain.

“In our first paper, we saw that the left and right cortex were larger in the choline-sufficient pigs,” he says. “After our second analysis, that makes sense. If you have a greater density of grey matter in the cortex, it is likely that brain region will have a greater volume as well.”

Decades of research has shown particular nutrients play specific roles in the neurodevelopmental process. The use of MRI technology has allowed researchers to identify the global influence of a specific nutrient on particular aspects of brain development. In an earlier study, the researchers found that another nutrient, iron, influenced aspects of both grey and white matter development.

“Our research shows that choline, like iron, does not appear to be specific to one part of brain development, it’s important for all of it,” Mudd says.

All of these results were for piglets born to choline-deficient mothers. But, as part of the study, some of the pigs from choline-deficient mothers were given adequate amounts of choline after birth. Was it enough to offset the deficiency during pregnancy?

The short answer is no, at least not for the brain. “Postnatal supplementation cannot correct for prenatal deficiency. It has to occur during development. We can’t recover that after the fact,” says Ryan Dilger, associate professor in the Department of Animal Sciences, Division of Nutritional Sciences, and Neuroscience Program at U of I.

However, another graduate researcher who collaborated on these papers led an earlier study on the same piglets in 2015. The study, led by Caitlyn Getty, showed lower brain weights in piglets from choline-deficient mothers, but her study focused more on overall health and metabolism of the piglets. From that perspective, it was postnatal choline intake that was most important, particularly for liver and kidney function.

pregnant woman

Choline, found in liver, eggs, wheat germ, and other foods, is an essential nutrient in human and animal diets. It’s required to make cell membranes, neurotransmitters, and myelin, the fatty sheath surrounding nerve cells. But most adults, including pregnant women, don’t consume enough. Image is in the public domain

The research, taken together, suggests a cellular-level mechanism to back up a 2013 study that concluded children born to mothers whose choline intake was well below the recommendation have lower academic outcomes by age seven.

“We know that the structural alteration is there, but it may not manifest in ways we can see until later in life. That’s why it’s important to think about this during gestation because the changes are occurring then,” Mudd says.

Dilger adds, “We’re not talking about an overt developmental disorder or saying if you don’t eat eggs when you’re pregnant, you cause a disorder. Instead, these are subtle pieces where we see individual variation and it could be related to your mother’s diet during pregnancy.”

About this neuroscience research article

Funding: USDA National Institute of Food and Agriculture provided the funding for this study.

Source: Lauren Quinn – University of Illinois
Publisher: Organized by NeuroscienceNews.com.
Image Source: NeuroscienceNews.com image is in the public domain.
Original Research: Open access research for “Maternal Dietary Choline Status Influences Brain Grey and White Matter Development in Young Pigs” by Austin T Mudd, Caitlyn M Getty, and Ryan N Dilger in Current Developments in Nutrition. Published online March 21 2018.
doi:10.1093/cdn/nzy015

Cite This NeuroscienceNews.com Article
University of Illinois “Prenatal Choline Intake Increases Gray and White Matter: Piglet Study.” NeuroscienceNews. NeuroscienceNews, 27 March 2018.
<http://neurosciencenews.com/choline-white-gray-matter-8697/>.
University of Illinois (2018, March 27). Prenatal Choline Intake Increases Gray and White Matter: Piglet Study. NeuroscienceNews. Retrieved March 27, 2018 from http://neurosciencenews.com/choline-white-gray-matter-8697/
University of Illinois “Prenatal Choline Intake Increases Gray and White Matter: Piglet Study.” http://neurosciencenews.com/choline-white-gray-matter-8697/ (accessed March 27, 2018).

Abstract

Maternal Dietary Choline Status Influences Brain Grey and White Matter Development in Young Pigs

Background
Choline is an essential nutrient that is pivotal to proper brain development. Research in animal models suggests that perinatal choline deficiency influences neuron development in the hippocampus and cortex, yet these observations require invasive techniques.

Objective
This study aimed to characterize the effects of perinatal choline deficiency on grey and white matter development using non-invasive neuroimaging techniques in the young pig.

Methods
During the last 64 days of the 114-day gestation period Yorkshire sows were provided a choline-sufficient (CS) or choline-deficient (CD) diet, analyzed to contain 1,214 mg or 483 mg total choline/kg diet, respectively. Upon farrowing, pigs (Sus scrofa domesticus) were allowed colostrum consumption for up to 48 hours, were further stratified into postnatal treatment groups, and were provided either CS or CD milk replacers, analyzed to contain 1,591 mg or 518 mg total choline/kg diet, respectively, for 28 days. At 30 days of age, pigs were subjected to magnetic resonance imaging procedures to assess brain development. Grey and white matter development was assessed through voxel-based morphometry (VBM) and tract-based spatial statistics (TBSS), to assess the effects of prenatal and postnatal dietary choline status.

Results
Voxel-based morphometry analysis indicated prenatally CS pigs exhibited increased (P < 0.01) grey matter in the left and right cortex compared with prenatally CD pigs. Analysis of white matter indicated prenatally CS pigs exhibited increased (P < 0.01) white matter in the internal capsule, putamen-globus pallidus, and right cortex compared with prenatally CD pigs. No postnatal effects (P > 0.05) of choline status were noted for VBM analyses of grey and white matter. Tract-based spatial statistics also revealed no significant effects (P > 0.05) of prenatal or postnatal choline status for diffusion values along white matter tracts.

Conclusions
Observations from this study suggest that prenatal choline deficiency results in altered cortical grey matter and reduced white matter in the internal capsule and putamen of young pigs. Using non-invasive neuroimaging techniques, results from our study indicate prenatal choline deficiency greatly alters grey and white matter development in the pig, thereby providing a translational assessment that may be used in clinical populations.

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