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Updated: Feb 7, 2026
Controlled Cortical Impact Model for Traumatic Brain Injury
Published on: August 5, 2014
DNA hydroxymethylation mediated traumatic spinal injury by influencing cell death-related gene expression
Hao Sun1,2,3, Zhigang Miao4,5, Hua Wang1,3
1Department of Orthopedics, Clinical Medical College of Yangzhou University, Yangzhou, China.
Abstract:
Spinal cord injury (SCI) is a serious neurological disease, often leading to segmental injury following severe limb dysfunction. Recent studies showed that epigenetic regulation is involved in the pathogenesis of SCI. In this study, we examined the change in 5-hydroxymethylcytosine (5hmC), a mechanism of demethylation, and its role in SCI in rats. We found that global 5hmC modification significantly increased in traumatic spinal cord tissues. Ten-eleven translocation (Tet) enzymes are the limiting-rate enzyme to catalyze the conversion of 5-methylcytosine to 5hmC. In our study, the data indicated that Tet2, but not Tet1 and Tet3, significantly increased in traumatic spinal cord tissues. Further, we treated rats with SC-1, a Tet2 expression inhibitor. SC-1 increased necrotic volume after SCI. To further demonstrate that the damage caused by SC-1 was related to DNA 5hmC, we examined the messenger RNA (mRNA) expression of many genes that related to cell death and cell survival. Our data showed that the 5hmC levels were related to the mRNA levels of these genes. In conclusion, targeting Tet2 to cause change in 5hmC levels in cell death-related genes may be new therapeutic strategy for the treatment of SCI.
Insights
Epigenetic regulation via 5-hydroxymethylcytosine (5hmC) is crucial in spinal cord injury (SCI). Inhibiting Tet2, an enzyme regulating 5hmC, worsened SCI outcomes in rats, suggesting Tet2 is a potential therapeutic target.
Area of Science:
- Neuroscience
- Epigenetics
- Molecular Biology
Background:
- Spinal cord injury (SCI) causes significant limb dysfunction.
- Epigenetic mechanisms, including DNA demethylation, are implicated in SCI pathogenesis.
- 5-hydroxymethylcytosine (5hmC) is a key epigenetic mark involved in demethylation.
Purpose of the Study:
- To investigate the role of 5hmC and Ten-eleven translocation (Tet) enzymes in SCI.
- To determine the effect of Tet2 inhibition on SCI outcomes.
Main Methods:
- Assessed global 5hmC levels and Tet enzyme expression (Tet1, Tet2, Tet3) in rat spinal cord tissues post-injury.
- Administered a Tet2 inhibitor (SC-1) to rats with SCI.
- Analyzed mRNA expression of cell death and survival genes.
Main Results:
- Global 5hmC levels and Tet2 expression significantly increased in traumatic spinal cord tissues.
- Tet2 inhibition with SC-1 exacerbated necrotic volume after SCI.
- 5hmC levels correlated with the mRNA expression of genes involved in cell death and survival.
Conclusions:
- Tet2-mediated epigenetic regulation of 5hmC plays a critical role in SCI.
- Targeting Tet2 to modulate 5hmC levels in cell death-related genes presents a potential therapeutic strategy for SCI treatment.
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