New Research Seeks to Understand Link Between Iron and Brain Development

Oct. 24, 2018

Pregnant woman with brainIron deficiency is the one of the most prevalent nutritional deficiencies in the world and affects mainly pregnant mothers and young children.  Numerous studies have found that mothers who have low iron levels during pregnancy, have a higher risk of giving birth to a child that develops cognitive impairments like autism, attention deficit syndrome, and learning disabilities. While the link between gestational iron deficiency (GID) and cognitive impairment in offspring is well establish, the mechanisms by which this occurs remain unknown.

Margot Mayer-Proschel, Ph.D., an associate professor in the University of Rochester Medical Center (URMC) Department of Biomedical Genetics and the Del Monte Institute for Neuroscience, has established animal models of GID and was the first to pinpoint the critical periods of gestation during which the developing central nervous system is most vulnerable to GID. Her laboratory recently demonstrated that nerve cells in the brains of animals born to iron deficient mice behave abnormally to excitatory brain stimuli and has shown that functional impairments cannot be restored by iron supplements later in life.

A new $2 million grant from the National Institute of Child Health & Human Development will build upon this pioneering work to understand more precisely the cellular mechanisms that cause iron deficiency to impair brain development. The new research will focus on specific sets of inhibitory neurons that, while small in number, play an important role in balancing the excitatory and inhibitory outputs that govern normal brain function. Preliminary work from Mayer-Proschel’s lab suggests that GID may trigger and overproduction in this population of cells leading to the disruption of brain signaling.

This new research also will seek to change the perception of the role of prenatal iron supplements and of how GID should be managed during pregnancy.  In order to provide sufficient iron to the developing fetus, the pregnant mother must increase consumption, which is primarily accomplished through multivitamins and supplements that contain iron. However, factors, such as obesity, diabetes, medications, and certain diets that contain high levels of whole grains, can prevent the body from absorbing iron. In addition, iron can cause severe nausea and constipation, causing many women to stop taking the supplement as long as they are not developing iron deficiency anemia, the most severe form of iron deficiency.

The research will also seek to develop a new method of determining fetal iron levels which, combined with a better understanding of the window during which iron is necessary for normal brain development, could help establish new standards of prenatal care. Currently, the mother’s blood is tested to determine iron levels, but this does not accurately reflect how much of the mineral is making its way to the fetus.  The new grant will enable the lab to develop biomarkers that could be used to identify iron deficiency in the developing fetus, allowing GID to be diagnosed and prevented at early stages of pregnancy.

Additional collaborators in the research project include Erhard Bieberich, Ph.D., from the University of Kentucky and Chris Proschel, Ph.D., in the URMC Department of Biomedical Genetics. The preliminary work done in Mayer-Proschel’s lab was supported in part by pilot funding from the Schmitt Program in Integrative Neuroscience.