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

• Published in: PloS one 2024-05, Vol.19 (5), p.e0303235-e0303235
• Main Authors: Yan, Lei, Li, Zihao, Li, Chuanbo, Chen, Jingyu, Zhou, Xun, Cui, Jiaming, Liu, Peng, Shen, Chong, Chen, Chu, Hong, Hongxiang, Xu, Guanhua, Cui, Zhiming
• Format: Article
• Language: English
• Subjects: Algorithms; Animals; Apoptosis; Autophagy; Bioinformatics; Calcium-binding protein; Cell culture; Cell death; Data mining; Excitotoxicity; Galectin 3 - genetics; Galectin 3 - metabolism; Gene expression; Genes; Glutamate; Glutamic acid; Glutamic Acid - metabolism; Heat-Shock Proteins - genetics; Heat-Shock Proteins - metabolism; Injury analysis; Interdisciplinary subjects; Learning algorithms; Machine Learning; Medical diagnosis; Molecular biology; Molecular Chaperones - genetics; Molecular Chaperones - metabolism; Neonates; Nervous system; Network analysis; Neurons; Neurons - metabolism; Penicillin; Protein interaction; Protein Interaction Maps; Protein-protein interactions; Proteins; Rats; Rats, Sprague-Dawley; Research methodology; S100 protein; Spinal cord; Spinal Cord - metabolism; Spinal Cord - pathology; Spinal cord injuries; Spinal Cord Injuries - genetics; Spinal Cord Injuries - metabolism; Spinal Cord Injuries - pathology; Tissue inhibitor of metalloproteinase 1; Transcriptomes
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0303235

Excitotoxicity represents the primary cause of neuronal death following spinal cord injury (SCI). While autophagy plays a critical and intricate role in SCI, the specific mechanism underlying the relationship between excitotoxicity and autophagy in SCI has been largely overlooked. In this study, we isolated primary spinal cord neurons from neonatal rats and induced excitotoxic neuronal injury by high concentrations of glutamic acid, mimicking an excitotoxic injury model. Subsequently, we performed transcriptome sequencing. Leveraging machine learning algorithms, including weighted correlation network analysis (WGCNA), random forest analysis (RF), and least absolute shrinkage and selection operator analysis (LASSO), we conducted a comprehensive investigation into key genes associated with spinal cord neuron injury. We also utilized protein-protein interaction network (PPI) analysis to identify pivotal proteins regulating key gene expression and analyzed key genes from public datasets (GSE2599, GSE20907, GSE45006, and GSE174549). Our findings revealed that six genes-Anxa2, S100a10, Ccng1, Timp1, Hspb1, and Lgals3-were significantly upregulated not only in vitro in neurons subjected to excitotoxic injury but also in rats with subacute SCI. Furthermore, Hspb1 and Lgals3 were closely linked to neuronal autophagy induced by excitotoxicity. Our findings contribute to a better understanding of excitotoxicity and autophagy, offering potential targets and a theoretical foundation for SCI diagnosis and treatment.