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  4. Integrated transcriptomic and metabolomic profiling reveals dysregulation of purine metabolism during the acute phase of spinal cord injury in rats

Integrated transcriptomic and metabolomic profiling reveals dysregulation of purine metabolism during the acute phase of spinal cord injury in rats

Front. Neurosci., 2022 · DOI: 10.3389/fnins.2022.1066528 · Published: November 23, 2022

Spinal Cord InjuryNeurologyBioinformatics

Simple Explanation

This study uses transcriptomics and metabolomics to understand metabolic changes after spinal cord injury (SCI) in rats. SCI disrupts the spinal cord's microenvironment, affecting nerve repair. By analyzing gene expression (transcriptomics) and metabolites (metabolomics), researchers aim to identify pathways that could be targeted to promote nerve regeneration. The study found that SCI significantly alters metabolites and gene expression in the acute phase. Specifically, purine metabolism was significantly dysregulated at both gene and metabolite levels. This dysregulation could impact energy metabolism and increase oxidative stress, hindering nerve repair. These findings suggest that targeting purine metabolism could be a potential therapeutic strategy for SCI. Understanding these complex molecular mechanisms may lead to better treatments for nerve repair and regeneration after SCI.

Study Duration
Not specified
Participants
28 adult male Sprague-Dawley (SD) rats
Evidence Level
Level Not specified, Animal Study

Key Findings

  • 1
    Histological analysis showed significant alterations in the microenvironment of the spinal cord after acute SCI, including poorly demarcated gray and white matter, cavities, and necrotic tissues. Locomotor function was also significantly reduced in rats with SCI.
  • 2
    Metabolomics analysis revealed that 360 metabolites were highly altered during the acute phase of SCI, with 310 being up-regulated and 50 being down-regulated. These differential metabolites were mainly enriched in arginine and proline metabolism, D-glutamine and D-glutamate metabolism, purine metabolism, and biosynthesis of unsaturated fatty acids.
  • 3
    Integrative analysis of transcriptomic and metabolomic data revealed significant dysregulation of purine metabolism at both the gene and metabolite levels during the acute phase of SCI, involving 48 differential genes and 16 differential metabolites.

Research Summary

This study integrated transcriptomic and metabolomic data to investigate metabolic dysregulation in the acute phase of spinal cord injury (SCI) in rats. The researchers aimed to identify potential molecular pathways involved in metabolic dysregulation to aid in developing future nerve repair and regeneration strategies. The study revealed significant alterations in both gene expression and metabolite profiles in the injured spinal cord. Metabolomics analysis showed 360 altered metabolites, while transcriptomics identified 5,963 differentially expressed genes. Integrative analysis highlighted the dysregulation of purine metabolism as a key finding. The dysregulation of purine metabolism could seriously affect the energy metabolism of the injured microenvironment and increase oxidative stress, hindering nerve repair and regeneration. These findings contribute to a better understanding of the pathological mechanisms in the acute phase of spinal cord injury.

Practical Implications

Therapeutic Target Identification

Identifies purine metabolism as a potential therapeutic target for SCI, which could lead to novel treatments focused on modulating this pathway to promote nerve repair.

Improved Understanding of SCI Pathophysiology

Provides a deeper understanding of the molecular mechanisms underlying SCI, which can inform the development of more effective and targeted interventions.

Multi-element Treatment Approaches

Supports a shift from single-element to multi-element, complex networked repair approaches for SCI, acknowledging the intricate nature of the injury and the need for comprehensive treatment strategies.

Study Limitations

  • 1
    Small sample size
  • 2
    Difference of each single omics platform
  • 3
    The role of these genes and metabolites in the pathophysiology of SCI requires further investigation

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