Administration of Tamoxifen Can Regulate Changes in Gene Expression during the Acute Phase of Traumatic Spinal Cord
Eibar E Cabrera-Aldana1, Yalbi I Balderas-Martinez2, Rafael Velázquez-Cruz3
1Department of Genomics Medicine, National Institute of Rehabilitation (INR), Calzada Mexico-Xochimilco 289, Arenal de Guadalupe, Mexico City 14389, Mexico.
Abstract:
Traumatic spinal cord injury (SCI) causes irreversible damage leading to incapacity. Molecular mechanisms underlying SCI damage are not fully understood, preventing the development of novel therapies. Tamoxifen (TMX) has emerged as a promising therapy. Our aim was to identify transcriptome changes in the acute phase of SCI and the effect of Tamoxifen on those changes in a rat model of SCI. Four groups were considered: (1) Non-injured without TMX (Sham/TMX-), (2) Non-injured with TMX (Sham/TMX+), (3) injured without TMX (SCI/TMX-), and (4) injured with TMX (SCI/TMX+). Tamoxifen was administered intraperitoneally 30 min after injury, and spinal cord tissues were collected 24 h after injury. Clariom S Assays Array was used for transcriptome analysis. After comparing Sham/TMX- versus SCI/TMX-, 708 genes showed differential expression. The enriched pathways were the SCI pathway and pathways related to the inflammatory response. When comparing SCI/TMX- versus SCI/TMX+, only 30 genes showed differential expression, with no pathways enriched. Our results showed differential expression of genes related to the inflammatory response after SCI, and Tamoxifen seems to regulate gene expression changes in Ccr2 and Mmp12. Our study contributes data regarding the potential value of tamoxifen as a therapeutic resource for traumatic SCI during the acute phase.
Insights
Traumatic spinal cord injury (SCI) triggers inflammation and gene changes. Tamoxifen (TMX) shows potential in regulating these acute-phase responses, offering a possible therapeutic avenue for SCI.
Area of Science:
- Neuroscience
- Molecular Biology
- Pharmacology
Background:
- Traumatic spinal cord injury (SCI) results in permanent damage and functional loss.
- The molecular underpinnings of SCI are not fully elucidated, hindering therapeutic development.
- Tamoxifen (TMX) is being investigated as a potential therapeutic agent for SCI.
Purpose of the Study:
- To investigate transcriptome alterations during the acute phase of SCI.
- To evaluate the impact of Tamoxifen (TMX) on these gene expression changes in a rat model.
- To identify molecular pathways affected by SCI and TMX treatment.
Main Methods:
- Transcriptome analysis using Clariom S Assays Array in a rat model of SCI.
- Four experimental groups: Sham/TMX-, Sham/TMX+, SCI/TMX-, and SCI/TMX+.
- TMX administered intraperitoneally 30 minutes post-injury; spinal cord tissues collected 24 hours post-injury.
Main Results:
- SCI induced differential expression in 708 genes compared to non-injured controls.
- Enriched pathways included the SCI pathway and inflammatory response pathways.
- TMX treatment in SCI rats resulted in differential expression of only 30 genes, notably affecting Ccr2 and Mmp12, with no enriched pathways.
Conclusions:
- SCI significantly alters gene expression, particularly inflammatory pathways, in the acute phase.
- Tamoxifen (TMX) appears to modulate specific gene expression changes, including Ccr2 and Mmp12, following acute SCI.
- These findings suggest TMX's potential as a therapeutic intervention for acute traumatic spinal cord injury.
