Maternal dietary deficiencies in folic acid or choline reduce primary neuron viability after exposure to hypoxia through increased levels of apoptosis.

Objective: Ischemic stroke is the leading cause of death and disability globally. By addressing modifiable risk factors, particularly nutrition, the prevalence of stroke and its dire consequences can be mitigated. One-carbon (1C) metabolism is a critical biosynthetic process that is involved in neural tube closure, DNA synthesis, plasticity, and cellular proliferation. Folates and choline are two active components of 1C metabolism. We have previously demonstrated that maternal dietary deficiencies during pregnancy and lactation in folic acid or choline result in worse stroke outcomes in offspring. However, there is insufficient data to understand the neuronal mechanisms involved.Methods: Using C57Bl/6J female mice maintained on control, folic acid (0.3 mg/kg) or choline (choline bitrate 300 mg/kg) deficient diets we collected embryonic primary neurons from offspring and exposed them to hypoxic conditions for 6 hours. To determine whether increased levels of either folic acid or choline can rescue reduced neuronal viability, we supplemented cell media with folic acid and choline prior to and after exposure to hypoxia.Results: Our results suggest that maternal dietary deficiencies in either folic acid or choline during pregnancy negatively impacts offspring neuronal viability after hypoxia. Furthermore, increasing levels of folic acid (250 mg/ml) or choline chloride (250 mg/ml) prior to and after hypoxia have a beneficial impact on neuronal viability.Conclusion: The findings contribute to our understanding of the intricate interplay between maternal dietary factors, 1C metabolism, and the outcome of offspring to hypoxic events, emphasizing the potential for nutritional interventions in mitigating adverse outcomes.