BE-62 Investigating the Effects of L-Methylfolate on Gene Expression in SH-SY5Y Cells Following Folic Acid Treatment
SCURS Disciplines
Cell Biology
Document Type
Poster Presentation
Abstract
Folate (Vitamin B9) is an essential nutrient which is involved in DNA synthesis and amino acid metabolism. When it comes to fetal development and neurological function, folate is vital. In medicine, folic acid (FA) supplementation is widely recommended to pregnant women for preventing neural tube defects, however, concerns have been raised about its bioavailability, specifically in individuals with methyltetrahydrofolate reductase (MTHFR) polymorphisms. L-methylfolate (L-MTHF) is the bioactive form of folate and has been suggested to be a better alternative. L-MTHF is synthesized by the body through FA metabolism using MTHFR, but less L-MTHF would be made in persons with mutated MTHFR. Excess FA intake has been linked to epigenetic alterations and neuronal abnormalities associated with neurodevelopmental disorders such as autism. In unpublished data from our lab; notably, when treating with FA for 48 hours followed by L-MTHF for 48 hours, there was a reversal of the alterations to autophagy and dendritic spines induced by FA, suggesting a potential restoration effect for L-MTHF. However, there is only limited research on whether L-MTHF supplementation can reverse these FA-induced changes. Our study examines the impact of L-MTHF on gene expression of epigenetic-modifying genes and autophagy-related genes in SH-SY5Y neuronal cells following FA exposure. L-MTHF treatment alone was also assayed to determine if L-MTHF alone affected expression of our genes of interest. Cells were cultured and assigned to various treatment groups, including prolonged FA exposure (92 hours), FA withdrawal (FA 48 hours + no treatment 48 hours), and FA supplementation followed by L-MTHF (FA 48 hours + L-MTHF 48 hours). Shorter experiments (48-hour treatments) were performed using a control, FA treatment, and L-MTHF treatment to determine L-MTHF’s effects alone. RNA was isolated via Trizol extraction, followed by cDNA synthesis and qPCR to assess gene expression of epigenetic modifying genes and autophagy-related genes. Our findings highlight the need for further investigation into the possible therapeutic implications of L-MTHF supplementation, particularly for those with MTHFR polymorphisms or those at risk for FA-related neurodevelopmental effects. Future research should focus on studying the molecular mechanisms for L-MTHF’s effects and its potential applications in prenatal and neurodevelopmental health. These findings contribute to the growing discussion on folate metabolism, supplementation strategies, and the broader implications for maternal and fetal health.
Keywords
Folate, L-Methylfolate, Autism, Gene Expression, Epigenetics, Autophagy
Start Date
11-4-2025 9:30 AM
Location
University Readiness Center Greatroom
End Date
11-4-2025 11:30 AM
BE-62 Investigating the Effects of L-Methylfolate on Gene Expression in SH-SY5Y Cells Following Folic Acid Treatment
University Readiness Center Greatroom
Folate (Vitamin B9) is an essential nutrient which is involved in DNA synthesis and amino acid metabolism. When it comes to fetal development and neurological function, folate is vital. In medicine, folic acid (FA) supplementation is widely recommended to pregnant women for preventing neural tube defects, however, concerns have been raised about its bioavailability, specifically in individuals with methyltetrahydrofolate reductase (MTHFR) polymorphisms. L-methylfolate (L-MTHF) is the bioactive form of folate and has been suggested to be a better alternative. L-MTHF is synthesized by the body through FA metabolism using MTHFR, but less L-MTHF would be made in persons with mutated MTHFR. Excess FA intake has been linked to epigenetic alterations and neuronal abnormalities associated with neurodevelopmental disorders such as autism. In unpublished data from our lab; notably, when treating with FA for 48 hours followed by L-MTHF for 48 hours, there was a reversal of the alterations to autophagy and dendritic spines induced by FA, suggesting a potential restoration effect for L-MTHF. However, there is only limited research on whether L-MTHF supplementation can reverse these FA-induced changes. Our study examines the impact of L-MTHF on gene expression of epigenetic-modifying genes and autophagy-related genes in SH-SY5Y neuronal cells following FA exposure. L-MTHF treatment alone was also assayed to determine if L-MTHF alone affected expression of our genes of interest. Cells were cultured and assigned to various treatment groups, including prolonged FA exposure (92 hours), FA withdrawal (FA 48 hours + no treatment 48 hours), and FA supplementation followed by L-MTHF (FA 48 hours + L-MTHF 48 hours). Shorter experiments (48-hour treatments) were performed using a control, FA treatment, and L-MTHF treatment to determine L-MTHF’s effects alone. RNA was isolated via Trizol extraction, followed by cDNA synthesis and qPCR to assess gene expression of epigenetic modifying genes and autophagy-related genes. Our findings highlight the need for further investigation into the possible therapeutic implications of L-MTHF supplementation, particularly for those with MTHFR polymorphisms or those at risk for FA-related neurodevelopmental effects. Future research should focus on studying the molecular mechanisms for L-MTHF’s effects and its potential applications in prenatal and neurodevelopmental health. These findings contribute to the growing discussion on folate metabolism, supplementation strategies, and the broader implications for maternal and fetal health.