Influence of Dietary Folic Acid on Methylenetetrahydrofolate Reductase (MTHFR) as a Biomarker of Down Syndrome in the Ts65Dn Mouse Model: Phases 1 and 2

Abstract

The relationship between folic acid and Down Syndrome (DS) is one that demands further inquiry to establish a diet and genetic interaction. In this multiphase study, we are examining cognitive, behavioral and biochemical signs of dietary changes of folic acid in the DS mouse model. In Phase 1, 20 non-genetic mice were cared for over 10 weeks; half of the mice were fed a folic acid deficient diet. In Phase 2, 20 mice, (10 DS mice and 10 non-genetic mice) were cared for until the age of 4.5 months; all mice were fed a diet with adequate folic acid. At 10 and 14 weeks, nestlet tests were administered. Blood samples were collected and an assay was run to measure Methylenetetrahydrofolate Reductase (MTHFR). In Phases 1 and 2 of this project, the physiological stability of non-genetic mouse models with dietary changes, the baseline behavioral and cognitive activity of the DS mouse model, and the baseline biochemical measurements of MTHFR were established. Phase 1 (summer 2014) established that, with a deficiency of folic acid in the diet, the mice continue to gain weight steadily and fragility of the mouse model does not increase. In Phase 2 (fall 2014), it was established that there was a behavioral difference between the DS mouse model and the non-genetic mouse as measured by nestlet testing (p=0.000). Additionally, Phase 2 established that there was no statistical significance between the DS mouse model and the non-genetic mouse model (p=0.8). This verified that when fed the same diet, there is no difference in MTHFR activity in the DS mouse model and the non-genetic mouse. Phase 1 and Phase 2 results have contributed to the development of our Phase 3 dietary intervention with high and low folic acid and the changes in MTHFR