Researchers Link Prenatal Fructose Exposure to Reduced Adult Neurogenesis

Nutritional imbalance during pregnancy can have long-lasting effects on the health status and disease susceptibility of the offspring. As such, high fructose intake through sweetened food and beverages in pregnant women has been associated with an increased susceptibility to diabetes and cardiovascular disease, as well as neurological and cognitive impairments in the offspring. Currently, it is not well understood how early life exposure to fructose has such long-lasting effects on the cellular and molecular level. 

In a recent paper published in Stem Cell Reports, Hiroya Yamada's team from Fujita Health University School of Medicine, Toyoake, Japan found that the performance of adult rats in learning and memory tests was impaired when the rats had been exposed to high fructose in before birth by feeding their mothers with high fructose corn syrup. Furthermore, neurogenesis, which is the generation of new neurons from neural stem cells (NSCs), in distinct regions of the brain involved in learning and cognition was reduced in those rats. Further, Yamada's group discovered distinct changes in NSCs after high fructose exposure, which included reduced cell division and impaired generation of new neurons, and altered gene expression. 

To explain why prenatal high fructose exposure can have such long-lasting effects on NSCs, the researchers profiled the so-called epigenetic changes, which are chemical imprints on the DNA controlling gene activity. Strikingly, prenatal high fructose exposure introduced distinct epigenetic changes in fetal NSCs which persisted into adulthood and which deregulated the activity of genes important for adult neurogenesis. Restoring normal expression of those genes improved the function of high fructose-exposed NSCs.

This research illustrates how early-life exposure to an adverse environment, e.g. an imbalanced maternal nutrition, can have long-lasting effects on brain development and function by changing the epigenetic regulation of gene activity in NSCs. Importantly, although epidemiological studies in human populations show similar correlations, further studies will be required to test if human NSCs are affected by high fructose and other environmental stressors in similar ways.

Our study suggests that neural stem cells may retain a biological memory of maternal nutrition during pregnancy. This may help explain how a transient prenatal dietary imbalance can lead to long-lasting changes in brain development and function."

Hiroya Yamada, Fujita Health University School of Medicine