Betaine restores epigenetic control and supports neuronal mitochondria in the cuprizone mouse model of multiple sclerosis

Figures & data

Figure 1. Schematic depicts methionine metabolism and the BHMT-betaine methylation pathway.

Figure 2. BHMT is expressed in neurons where it interacts with chromatin and regulates HMT activity.

Table 1. BHMT is enriched at regulatory regions of mitochondrial genes.

KEGG pathway	Number of genes enriched for BHMT	p value
1. Metabolism (hsa01100)	175/1243	9.71e-19
2. Parkinson’s disease (hsa05012)	51/142	4.08e-18
3. Oxidative phosphorylation (hsa00190)	48/133	2.95e-13
4. Alzheimer’s disease (hsa05010)	46/168	7.13e-13
5. Huntington’s disease (hsa05016)	46/193	3.93e-11

Figure 3. ChIP-seq shows that BHMT is enriched at transcriptional regulators of mitochondrial genes and at mitochondrial genes.

Figure 4. The cuprizone mouse model mimics the activation of microglia, increased RNS, and methionine metabolism changes exhibited in MS.

Figure 5. Betaine treatment rescues epigenetic control and supports mitochondria.

Figure 6. Betaine alleviates sensorimotor disability in cuprizone mice.

Figure 7. Model for BHMT-betaine mediated regulation of mitochondrial gene expression.