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  4. Hspb1 and Lgals3 in spinal neurons are closely associated with autophagy following excitotoxicity based on machine learning algorithms

Hspb1 and Lgals3 in spinal neurons are closely associated with autophagy following excitotoxicity based on machine learning algorithms

PLOS ONE, 2024 · DOI: https://doi.org/10.1371/journal.pone.0303235 · Published: May 10, 2024

Spinal Cord InjuryNeurologyBioinformatics

Simple Explanation

This study investigates the relationship between excitotoxicity and autophagy in spinal cord injury (SCI). Excitotoxicity, caused by excessive glutamate levels, is a major cause of neuronal death after SCI. Autophagy, a cellular self-degradation process, plays a complex role in SCI. The researchers used machine learning to identify key genes involved in spinal cord neuron injury. They mimicked excitotoxic injury in rat spinal cord neurons using high concentrations of glutamic acid, then performed transcriptome sequencing and various bioinformatic analyses. The study found that certain genes (Anxa2, S100a10, Ccng1, Timp1, Hspb1, and Lgals3) were significantly upregulated in both in vitro and in vivo SCI models. Further analysis suggested that Hspb1 and Lgals3 are closely linked to neuronal autophagy induced by excitotoxicity.

Study Duration
Not specified
Participants
Neonatal Sprague-Dawley rats and healthy adult female Sprague-Dawley rats (8 weeks old, weighing 180–220 g)
Evidence Level
Not specified

Key Findings

  • 1
    Six genes—Anxa2, S100a10, Ccng1, Timp1, Hspb1, and Lgals3—were significantly upregulated in vitro in neurons subjected to excitotoxic injury and in rats with subacute SCI.
  • 2
    Hspb1 and Lgals3 were closely linked to neuronal autophagy induced by excitotoxicity.
  • 3
    The study identified a characteristic gene set comprising 195 candidate genes closely associated with excitotoxicity by employing WGCNA, DEG, and RF algorithms.

Research Summary

This study investigated the relationship between excitotoxicity and autophagy in SCI, using machine learning to identify key genes involved in neuronal injury. The researchers induced excitotoxic neuronal injury in vitro using high concentrations of glutamate and analyzed gene expression changes. The study identified six significantly upregulated genes (Anxa2, S100a10, Ccng1, Timp1, Hspb1, and Lgals3) in both in vitro and in vivo SCI models. Further analysis suggested that Hspb1 and Lgals3 are closely linked to neuronal autophagy induced by excitotoxicity. The findings suggest that Hspb1 and Lgals3 may represent novel targets for SCI treatment, enhancing the comprehension of excitotoxicity and autophagy processes in spinal cord neurons, thus providing new perspectives for SCI therapy.

Practical Implications

Diagnostic Potential

The six key genes (Anxa2, S100a10, Ccng1, Timp1, Hspb1, and Lgals3) could be potential diagnostic markers for SCI, aiding in the early detection and assessment of the injury's severity.

Therapeutic Targets

Hspb1 and Lgals3, identified as pivotal in regulating neuronal autophagy induced by excitotoxicity, may represent novel therapeutic targets for SCI. Modulating their activity could potentially mitigate neuronal damage and promote recovery.

Understanding SCI Mechanisms

The study contributes to a better understanding of the complex interplay between excitotoxicity and autophagy in SCI, offering a theoretical foundation for developing neuroprotective strategies.

Study Limitations

  • 1
    The specific mechanisms of Hspb1 and Lgals3 in neurons remain to be elucidated and requires further investigation.
  • 2
    The study acknowledges the complex and sometimes conflicting role of autophagy in SCI, highlighting the need for further research to understand the context-dependent effects of autophagy modulation.
  • 3
    Further investigation is needed to elucidate the impact of injury duration and severity on the neuronal death mechanisms.

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