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

Title

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

Creator

Singhal Naveen K; Sternbach Sarah; Fleming Sheila; Alkhayer Kholoud; Shelestak John; Popescu Daniela; Weaver Alyx; Clements Robert; Wasek Brandi; Bottiglieri Teodoro; Freeman Ernest J; McDonough Jennifer

Publisher

Epigenetics

Date

2020
2020-02

Description

Methionine metabolism is dysregulated in multiple sclerosis (MS). The methyl donor betaine is depleted in the MS brain where it is linked to changes in levels of histone H3 trimethylated on lysine 4 (H3K4me3) and mitochondrial impairment. We investigated the effects of replacing this depleted betaine in the cuprizone mouse model of MS. Supplementation with betaine restored epigenetic control and alleviated neurological disability in cuprizone mice. Betaine increased the methylation potential (SAM/SAH ratio), levels of H3K4me3, enhanced neuronal respiration, and prevented axonal damage. We show that the methyl donor betaine and the betaine homocysteine methyltransferase (BHMT) enzyme can act in the nucleus to repair epigenetic control and activate neuroprotective transcriptional programs. ChIP-seq data suggest that BHMT acts on chromatin to increase the SAM/SAH ratio and histone methyltransferase activity locally to increase H3K4me3 and activate transcriptional programs that support neuronal energetics. These data suggest that the methyl donor betaine may provide neuroprotection in MS where mitochondrial impairment damages axons and causes disability.

Rights

Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).

Format

Journal Article

Search for Full-text

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NEOMED College

NEOMED College of Pharmacy

NEOMED Department

Department of Pharmaceutical Sciences

Update Year & Number

March 2020 Update

Citation

Singhal Naveen K; Sternbach Sarah; Fleming Sheila; Alkhayer Kholoud; Shelestak John; Popescu Daniela; Weaver Alyx; Clements Robert; Wasek Brandi; Bottiglieri Teodoro; Freeman Ernest J; McDonough Jennifer, “Betaine restores epigenetic control and supports neuronal mitochondria in the cuprizone mouse model of multiple sclerosis.,” NEOMED Bibliography Database, accessed January 17, 2021, https://neomed.omeka.net/items/show/10989.

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