Dr. Steven Zeisel discusses how maternal intake of choline effects DNA methylation during development, and can lead to better memory. This interview was shot at the Keystone Symposia’s meeting on Nutrition, Epigenetics and Human Disease, 2013 held in Santa Fe, New Mexico
Choline Metabolism, DNA Methylation, and Memory
So I’m more and more believing that epigenetics in part, is there to allow the readjustment of metabolism when what the baby sees in utero is somehow different from what the baby gets once it’s delivered. And so we are studying the effect of nutrients on epigenetic marks and the effect of epigenetics on modifying nutrient metabolism.
And I work on a nutrient called choline. Many people in epigenetics have been thinking about folic acid and methylfolate as part of the donor and have been thinking less about choline and other sources of methyl groups.
And what we’ve been finding is that it’s an extremely important nutrient modifier of methylation and therefore of epigenetic marks. And so characterizing what makes people different in terms of choline metabolism would help us, in the future, to understand why people might be making different epigenetic marks.
Most of our work has been around trying to characterize why giving more choline during a very short period of pregnancy in rodent models results in a dramatic increase in neurogenesis in the hippocampus– neuroformation in the hippocampus. And that we can double the rate of neural progenitor cell proliferation in the fetal hippocampus by just feeding the mother, more or less, choline.
…so characterizing what makes people different in terms of choline metabolism would help us, in the future, to understand why people might be making different epigenetic marks.
And in trying to describe why, one of the hypotheses was that we were changing the epigenetic marks and we were able to show and publish that, indeed, baby rats– fetal rats, in their neural progenitor cells in their hippocampus, were methylating more when mother had a higher choline diet than when she had a lower choline diet.
And that methylation occurred in a specific gene called CDKN3 that acts as a brake on cell proliferation. And that the methylation certainly was consistent with changing the activity of that– the product of that gene and the rates of cell proliferation might be the explanation for why choline was such a good modifier of brain development.
These mice were exposed to a little extra choline in utero for five days. For the rest of their lives, perform about 30% better on memory testing, and in fact, never lose any memory. While the mice who are exposed to lower choline during those five days perform worse on memory testing when they’re young, but that gets worse as they get older. And they make more and more mistakes as they get older and become senile.
And so that’s been worked on by a number of investigators in behavior that we’ve complemented with biochemical and molecular biological studies to explain what’s going on and at the epigenetic and neural progenitor cell level.