DNA hydroxymethylation changes in response to spinal cord damage in a multiple sclerosis mouse model.

Abstract

Roles of DNA 5-hydroxymethylcytosine (5hmC) in myelin repair were investigated in an experimental autoimmune encephalomyelitis (EAE) mouse model via its regulation on BDNF. DNA 5hmC level and its limiting enzymes were detected in EAE mice. Global 5hmC modification, Tet1 and Tet2 significantly decreased in the spinal cord tissues of EAE mice. BDNF protein and mRNA decreased and were highly associated with BDNF 5hmC. Vitamin C, a Tet co-factor, increased global DNA 5hmC and reduced the neurological deficits at least by increasing BDNF5hmC modification and protein levels. Tet protein-mediated 5hmC modifications represent a critical target involved in EAE-induced myelin damage. Targeting epigenetic modification may be a therapeutic strategy for multiple sclerosis.