Yan Tang1,2,3, Man Luo1, Kailing Pan3, Tina Ahmad2, Ting Zhou2, Zhigang Miao3, Hang Zhou3, Hao Sun4, Xingshun Xu1,3, Michael Namaka2, Yongxiang Wang4,5. 1. Department of Neurology, The Second Affiliated Hospital of Soochow University, Suzhou City, PR China. 2. Faculty of Health Sciences, College of Pharmacy, University of Manitoba, Manitoba, Winnipeg R3E 3P4, Canada. 3. Institute of Neuroscience, Soochow University, Suzhou City, PR China. 4. Department of Orthopedics, Clinical Medical College, Yangzhou University, Yangzhou City, PR China. 5. Department of Orthopedics, Northern Jiangsu People's Hospital, Yangzhou City, PR China.
Abstract
AIM: Roles of DNA 5-hydroxymethylcytosine (5hmC) in myelin repair were investigated in an experimental autoimmune encephalomyelitis (EAE) mouse model via its regulation on BDNF. METHODS: DNA 5hmC level and its limiting enzymes were detected in EAE mice. RESULTS: 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 BDNF 5hmC modification and protein levels. CONCLUSION: 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.
AIM: Roles of DNA 5-hydroxymethylcytosine (5hmC) in myelin repair were investigated in an experimental autoimmune encephalomyelitis (EAE) mouse model via its regulation on BDNF. METHODS: DNA 5hmC level and its limiting enzymes were detected in EAE mice. RESULTS: 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 BDNF5hmC. Vitamin C, a Tet co-factor, increased global DNA 5hmC and reduced the neurological deficits at least by increasing BDNF5hmC modification and protein levels. CONCLUSION: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.