The impact of maternal dietary deficiencies in folic acid and choline on offspring neuronal function after hypoxia

Abstract

Ischemic stroke is an unmet medical need within the clinical population and is associated with significant mortality and morbidity. Nutrition is a modifiable risk factor for ischemic stroke. A maternal diet that provides adequate nutrition during pregnancy and lactation is vital to the neurodevelopment of offspring. Deficiencies in nutrients during fetal growth can lead to altered early life nutritional programming, such as spina bifida, a neural tube defect. There is an opportunity for advancing therapeutic intervention by completing additional research aimed at understanding the mechanistic impact of maternal nutrition on offspring ischemic stroke. Dietary deficiencies of one‐carbon (1C) metabolites have been associated with an increased risk for stroke. 1C metabolites include folic acid and choline which play a vital role in early life neurodevelopment. Data from our laboratory demonstrates that maternal dietary deficiencies in these vitamins and nutrients impact stroke outcome in 2‐month‐old male and female offspring, however, the mechanisms through which this occurs remain unknown. The aim of the present study was to investigate the impact of maternal dietary deficiencies in folic acid or choline on neuronal viability. This project used hypoxia as an in vitro model of stroke. Prior to mating, female mice were placed on a control, folic acid, or choline deficient diet for 4 weeks. Primary neurons were isolated from embryonic tissue, grown in culture, and exposed to hypoxia, after which cells were returned to normoxia. Twenty‐four hours after hypoxia, neuronal viability and apoptosis was measured in cultures. Our results demonstrate that offspring neurons from deficient mothers had reduced cell viability. There was also a change in the level of apoptosis between maternal dietary groups and treatments. These results suggest that a maternal dietary deficiency during pregnancy negatively impacts neurons after hypoxia.