Increased dietary levels of folic acid reduce survival and alters climbing behaviors 24 hours after hypoxia in male and female Drosophila melanogaster

Abstract

Hypoxia is a major component of ischemic stroke. The prevalence of ischemic stroke is expected to increase as the global population ages and risk factors, like obesity, are on the rise. Nutrition is a modifiable risk factor for ischemic stroke. Increased dietary intake of folic acid (FA) has become an increasing problem in the U.S and other countries as more people are consuming at or above the recommended daily amount of FA. The impact of too much dietary FA on hypoxia is not well understood. This study aimed to investigate how increased dietary levels of FA impact hypoxia outcomes using Drosophila melanogaster as a model. Adult female and male w1118 Drosophila melanogaster flies were placed on control (CD) and 100 {micro}M folic acid (FAD) diets. At 5 to 6 days old fruit fly progeny were exposed to hypoxia for two hours prior to returning to normoxic conditions. We observed escape behavior in hypoxia larvae, confirming exposure to hypoxia. Using liquid chromatography-tandem mass spectrometry, elevated FA levels were observed in FAD compared to controls. We report increased acute hypoxia-induced mortality in FAD flies. Furthermore, FAD flies were not motivated to climb after hypoxia. Under normoxic conditions FAD flies had a higher velocity when descending during a climb. Interestingly, there was no impact of FA on apoptosis in brain tissue post-hypoxia. Together these data suggest that increase dietary intake of FA can have negative health outcomes after hypoxia. HighlightsO_LIHigh dietary folic acid and hypoxia increased mortality at the 24-hour time point. C_LIO_LIHypoxia and folic acid decreased motivation to climb and reduced movement in flies. C_LIO_LINo effect of hypoxia and folic acid on apoptosis levels in the fly brain tissue. C_LI