Excess folic acid as a potential competitor of glutamate may interfere with neural development

Folic acid, Vitamin B9, is strongly advised as a supplement taken by pregnant woman to maintain the health of the embryo, and deficiency increases the risk of neural tube defects. However, a safe upper limit of folate to consume has not been established, and an excess of dietary folate may interfere with neurodevelopmental metabolism, increasing the risk of adverse outcomes, including autism spectrum disorder (ASD). It has been suggested that folate affects connectivity among neurons as the brain develops. Glutamate is important in the regulation of neural tissue development, as it is a common excitatory neurotransmitter that binds to synaptic membranes. Because it is so structurally similar to folic acid, it may compete for binding sites on neurons within developing tissues, affecting connectivity of neurons during embryonic brain development. This experiment tested the effects of adding excess folate, glutamate or both to cultures of developing neural tissue to determine whether embryonic neuronal behavior is altered. An inverted phase microscope with a heated stage was used to collect time-lapse images of a region of extending neurites with growth cones. After 30 images (one per minute), a known concentration of folate, glutamate or both was added to the dish and 30 more images were collected. Images were analyzed using ImageJ software, and alterations in exploratory behavior of the neurites with growth cones were recorded. The data suggests that excess glutamate can overcome an inhibition of area change per minute by excess folate, which authenticates a mechanism of inhibition of neural development by excess folate. This supports the hypothesis of underconnectivity during brain development leading to ASD