2023 - Full Presentation Schedule
Investigation of L-Methylfolate's effects on Folic Acid treated and differentiated human neuronal cells
Start Date
31-3-2023 2:30 PM
End Date
31-3-2023 2:45 PM
Location
CASB 104 - Anatomy and Cell and Molecular Biology
Document Type
Presentation
Abstract
Autism Spectrum Disorders (ASD) is a group of neurodevelopment disorders known to have an epigenetic or environmental component. Environmental components can include stress and diet. Folic acid (FA) is a dietary factor that is consumed in large quantities as of late due to its availability in fortified grains and beverages.
FA affects epigenetics through one-carbon metabolism and was previously shown to induce an increased number of dendritic spines in a human neuronal cell line (SH-SY5Y cells) within our lab. Increased dendritic spines is a phenotype of autism patients’ cortical brain tissues, along with a reduction in autophagy.
Notably, many ASD patients have a mutation in the MTHFR (Methylenetetrahydrofolate reductase). L-Methylfolate is a lesser known “folate” which is an active derivative of FA just beyond the metabolic step that utilizes the MTHFR enzyme. Previously, our lab treated a human neuronal cell line with a 2x folic acid dose (48 hours) followed by another 48 hour folic acid treatment or a 48 hour L-Methylfolate treatment. L-Methylfolate alone showed no negative effects on dendritic spines or autophagy rates. When L-Methylfolate followed a 48 hour folic acid treatment, L-Methylfolate corrected excess dendritic spines and loss of autophagy induced by the 2x folic acid treatment. However, our former studies were in undifferentiated neurons, mimicking neurons that are not yet post-mitotic.
To mimic the effects of L-Methylfolate in post-mitotic neurons as those seen past embryonic development, we repeated our experiments after a 7-day 5uM retinoic acid differentiation. Retinoic acid is used in SH-SY5Y cells for differentiation into defined neural phenotypes, and thus more representative of young human cells.
I hypothesize that L-Methylfolate will still reverse the decreased autophagy and increased dendritic spines brought on by the 2x folic acid treatment in differentiated, post-mitotic SH-SY5Y cells. Our findings indicate that L-Methylfolate should be further investigated in complete physiological systems as a holistic remedy for ASD patients.
Investigation of L-Methylfolate's effects on Folic Acid treated and differentiated human neuronal cells
CASB 104 - Anatomy and Cell and Molecular Biology
Autism Spectrum Disorders (ASD) is a group of neurodevelopment disorders known to have an epigenetic or environmental component. Environmental components can include stress and diet. Folic acid (FA) is a dietary factor that is consumed in large quantities as of late due to its availability in fortified grains and beverages.
FA affects epigenetics through one-carbon metabolism and was previously shown to induce an increased number of dendritic spines in a human neuronal cell line (SH-SY5Y cells) within our lab. Increased dendritic spines is a phenotype of autism patients’ cortical brain tissues, along with a reduction in autophagy.
Notably, many ASD patients have a mutation in the MTHFR (Methylenetetrahydrofolate reductase). L-Methylfolate is a lesser known “folate” which is an active derivative of FA just beyond the metabolic step that utilizes the MTHFR enzyme. Previously, our lab treated a human neuronal cell line with a 2x folic acid dose (48 hours) followed by another 48 hour folic acid treatment or a 48 hour L-Methylfolate treatment. L-Methylfolate alone showed no negative effects on dendritic spines or autophagy rates. When L-Methylfolate followed a 48 hour folic acid treatment, L-Methylfolate corrected excess dendritic spines and loss of autophagy induced by the 2x folic acid treatment. However, our former studies were in undifferentiated neurons, mimicking neurons that are not yet post-mitotic.
To mimic the effects of L-Methylfolate in post-mitotic neurons as those seen past embryonic development, we repeated our experiments after a 7-day 5uM retinoic acid differentiation. Retinoic acid is used in SH-SY5Y cells for differentiation into defined neural phenotypes, and thus more representative of young human cells.
I hypothesize that L-Methylfolate will still reverse the decreased autophagy and increased dendritic spines brought on by the 2x folic acid treatment in differentiated, post-mitotic SH-SY5Y cells. Our findings indicate that L-Methylfolate should be further investigated in complete physiological systems as a holistic remedy for ASD patients.