The nutrition that mothers get during pregnancy could have lifelong effects on the health of their children. This is particularly true of brain development, especially as it relates to vitamin deficiencies and the development of mental disorders later in life.
Michael Georgieff, M.D., part of the U’s pediatrics faculty, and Yasushi Nakagawa, M.D., Ph.D., part of the neuroscience faculty, have a keen interest in healthy brain development. With Masonic support, they’re setting out to better understand the role of vitamin A in the developing brain and how deficiencies in this vitamin could lead to schizophrenia and other developmental brain disorders during adulthood.
Unraveling vitamin A in brain development
Brain development is a complex process involving many events, from the generation of neurons during cell division, to their migration to a permanent location in the brain. Georgieff and Nakagawa want to identify the steps that depend on vitamin A so that deficiencies that increase disease risk can be prevented during pregnancy and early in life.
“It’s been well established that a deficiency in vitamin A leads to an increased risk of mental disorders like schizophrenia later in life,” Nakagawa explains. “What’s not well known is the mechanism by which this happens and how a deficiency leads to a change in the structure and function of the brain, which then leads to certain behaviors.”
Nakagawa and Georgieff are launching their study with newborn and embryonic mice, which share many similarities with people when it comes to brain development and function. They are currently examining neuron migration in the brains of neonatal mice and will soon be testing them for behavioral abnormalities.
“We’re hoping these experiments will set the stage for discovering the critical period during which vitamin A is needed for proper brain development,” says Nakagawa. So far, he and Georgieff have discovered that when vitamin A is absent from the diet of pregnant mice it disrupts the development of a specific type of neurons in the cerebral cortex that are linked to higher cognitive function in both mice and people. But it’s still early, they caution, and if history is any indication there will be more discoveries to come. Georgieff likens the work to earlier efforts in understanding the impact of iron on the developing brain.
“For the longest time, it was thought that iron only affected certain types of neurons with certain types of transmitters. The world just sat there for a while and suddenly we discovered a second and third type, and so on,” Georgieff says. “Vitamin A is so ubiquitous and its receptors in the nucleus are so ubiquitous that it’s hard to believe there’s just one type of neuron that’s affected.”
After completing their mouse study, Nakagawa and Georgieff hope to apply for support from the National Institutes of Health (NIH) to look at vitamin A deficiency and brain development in people.
Ultimately, their findings could lead to significant milestones in improving health, including:
- Influencing new nutritional guidelines to ensure that women of child-bearing age receive enough vitamin A
- Identifying behavioral cues early in life, which could be precursors to schizophrenia
- Reversing schizophrenia and other brain disorders later in life through vitamin A treatment
“There’s a lot of cost to society in terms of lost education, lost jobs, and so on when you look at mental disorders. When you apply for an NIH grant, they want to see that you’re making an impact on these long-term societal challenges,” says Georgieff. “Our work will be an important part of this.”
Critical, transformative support
The developmental research that Nakagawa and Georgieff are leading, focused on early or in utero impacts on long-term health, is a relatively new area of study.
“Only about 10 percent of medical researchers think developmentally, where we look at current health issues being a function of problems or behaviors that occur early in childhood or in utero,” says Georgieff. “Literally everything you see downstream is a function of what happens earlier.”
When it comes to available funding, this translates into scarce resources for developmental research from entities like the NIH. “If you look at research dollars allocated by the NIH, 90 percent goes toward adult diseases,” Georgieff explains, which makes private support critical.
“Without Masonic funding, it would be impossible to do this research, it directly supports the people who are doing the experiments,” says Nakagawa. “It’s absolutely crucial.”
“There’s no other mechanism that has been as immediately transformative as Masonic support,” continues Georgieff. “It’s a real jumpstart.”