Abnormal DNA Methylation in Thoracic Spinal Cord Tissue Following Transection Injury

Medical Science Monitor, 2018 · DOI: 10.12659/MSM.913141 · Published: December 8, 2018

Simple Explanation

Spinal cord injury (SCI) is a serious condition that can lead to significant disabilities and high mortality rates. Currently, there are no truly effective treatments available. Abnormal DNA methylation, a process that can alter gene expression, is believed to play a role in SCI, affecting axonal regeneration and cell proliferation. This study used whole-genome bisulfite sequencing (WGBS) to examine changes in DNA methylation in rats following spinal cord transection. The goal was to identify key genes and signaling pathways that are affected by these changes, potentially offering new targets for epigenetic therapies. The researchers identified several genes with altered methylation patterns after SCI and found that these genes are involved in important processes like axon guidance, endocytosis, and immune signaling. These findings may provide valuable insights into the molecular mechanisms underlying SCI and could pave the way for novel therapeutic strategies.

Study Duration

8 weeks

Participants

18 adult female Wistar rats, divided into a sham group (n=9) and a SCI group (n=9)

Evidence Level

Animal Study

Key Findings

1
Following SCI, significant histological changes were observed, including cavities, necrotic tissue, and inflammatory cell infiltration. Motor function scores were also significantly reduced in the SCI group compared to the sham group.
2
Whole-genome bisulfite sequencing identified 96 differentially methylated genes (DMGs), with 50 being hypermethylated and 46 being hypomethylated. These DMGs were significantly enriched in pathways such as Axon Guidance, Endocytosis, T cell receptor signaling, and Hippo signaling.
3
qRT-PCR validation confirmed that hypermethylated genes were downregulated and hypomethylated genes were upregulated in the SCI group, supporting the WGBS data. Core genes identified include Csf2, Fars2, Synj2, Ppp3cc, Stat4, Pcsk2, Dnm3, and Hmgcll1.

Research Summary

This study investigated the epigenetic changes, specifically DNA methylation, in a rat model of spinal cord injury (SCI). The researchers performed whole-genome bisulfite sequencing to identify differentially methylated genes (DMGs) in the thoracic spinal cord tissue following transection injury. The analysis revealed 96 DMGs, including 50 hypermethylated and 46 hypomethylated genes. KEGG pathway analysis highlighted the Axon Guidance pathway, Endocytosis pathway, T cell receptor signaling pathway, and Hippo signaling pathway as significantly involved. These findings suggest that abnormal DNA methylation and key signaling pathways play a role in spinal cord injury. The identified core genes, such as Csf2, Dnm3, and others, may serve as potential therapeutic targets for SCI.

Practical Implications

Therapeutic Targets

The identified core genes (Csf2, Fars2, Synj2, Ppp3cc, Stat4, Pcsk2, Dnm3, and Hmgcll1) may represent potential therapeutic targets for the treatment of spinal cord injury.

Diagnostic Markers

The differentially methylated genes could potentially be used as biomarkers for more accurate diagnosis of spinal cord injury.

Drug Development

Understanding the role of these epigenetic changes may aid in the development of drug therapies aimed at alleviating neuropathic pain and promoting nerve repair after SCI.

Study Limitations

1
The study was conducted using rodent models, and further research is needed using primate models and human studies.
2
The study focused on the spinal cord but did not investigate epigenetic changes in the brain after SCI.
3
The study primarily investigated DNA methylation, and other epigenetic mechanisms such as histone modification and gene silencing were not fully explored.

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