BHMT expression constructs in neurons to determine if betaine increases H3K4me3 levels by activating BHMT activity

Decreased mitochondrial respiratory capacity has been reported in multiple sclerosis (MS), and evidence suggests a connection between the methionine metabolism cycle and this respiration. In the methionine metabolism cycle, enzyme betaine homocysteine methyltransferase (BHMT) is involved in converting homocysteine to methionine, with betaine acting as the methyl donor. Importantly, betaine has been reported in lower amounts in MS cortex, and betaine supplementation has even been shown to rescue mitochondrial respiratory capacity. The purpose of this study was to further investigate the role of nutrigenomics in MS by confirming the importance of the enzyme BHMT in the entrance of betaine into the methionine metabolism cycle. We made BHMT expression constructs that will be looked at in primary neurons. These constructs are wild type (WT) and BHMT mutant constructs that don’t have enzymatic activity. We will transfect these in neurons, treat with betaine, and measure levels of H3K4me3 by Western Blot to determine if betaine is increasing H3K4me3 by activating BHMT activity.