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