Featured Research

NRI Researcher Links Choline Deficiency to Impaired Brain Structure

September 06, 2016

Natalia Surzenko is part of a team of researchers at the UNC-Chapel Hill Nutrition Research Institute (NRI) located on the North Carolina Research Campus (NCRC) in Kannapolis focusing their efforts on brain development. Her current goal is to determine the role of choline as an essential nutrient for development of the cerebral cortex.

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Zeisel

The NRI’s director, Steven Zeisel, MD, PhD, was among the first scientists to discover that choline is an essential nutrient that is especially needed by pregnant women to ensure proper fetal development. Surzenko is building on his legacy by looking for specific structural changes in the brain caused by a low choline diet. In a recent study published in the FASEB Journal, Surzenko and her colleagues observed and measured in a mouse model the impact of a low-choline diet on neural progenitor cells through stimulation of a protein called epidermal growth factor receptor (EGFR).

A “sensitive window” of brain development

Neural progenitor cells are programmed to become part of the brain or central nervous system. Choline regulates EGFR expression in neural progenitor cells as a mechanism of brain development. In Suzenko’s study, she and her colleagues showed for the first time that a maternal diet low in choline leads to less proliferative progenitor cells in the cerebral cortex, which is the outer layer of the brain’s neural tissue.

Her study also found that the impact of choline deficiency on the brain occurs during a “sensitive window” of brain development and leads to reduced numbers of neural progenitor cells, a reduction in brain size and major defects in cortical layering.

“The effect is not corrected even if the animal is kept on a normal choline diet after being deficient,” Surzenko explained. “There is a permanent, long-lasting effect on the structure of the cerebral cortex.”

A collaborative effort

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Surzenko | Credit: UNC NRI

Surzenko was able to study the expression of EGFR protein thanks to confocal microscopy available just across the street from the NRI at the David H. Murdock Research Institute (DHMRI). The use of DHMRI’s confocal microscopy helped Surzenko determine that a low choline diet reduced EGFR receptor expression in neural progenitor cells both in whole brain samples and isolated neural progenitor cell samples.

“As a result of having fewer progenitor cells and of them dividing less, we are actually getting fewer neurons – cells that are the basic functional units of the central nervous system and communicate with each other across different brain regions,” she said.

What makes Surzenko’s findings even more pertinent is the prevalence of women who rely on dietary choline during pregnancy. “Around 45 percent of women carry a polymorphism in the gene required to produce choline during pregnancy as a response to estrogen, which makes them vulnerable to choline deficiency” Surzenko explained. “Without enough dietary choline, the developing fetuses in these mothers are at a risk for hindered brain development.”

What’s next?

Now that Surzenko and the NRI have shown the effect on choline deficiency during pregnancy in mice, they plan to examine whether or not the deficiency leads to behavioral differences in animals with abnormal cortex structure after birth and later in life. Then Surzenko will focus on making the research translatable to human pregnancies.

For more about the NRI and their research projects, please visit http://www.uncnri.org/.

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