Transcriptome Sequencing Reveals Molecular Characteristics of Spinal Cord Degeneration in MPTP-Induced Parkinson's...

Parkinson's disease (PD) involves not only the loss of dopaminergic neurons in the substantia nigra but also spinal cord degeneration. However, the molecular mechanisms of spinal cord degeneration remain unclear. This study investigated the spinal cord transcriptomic characteristics of MPTP-induced PD mice via transcriptome sequencing and weighted gene co-expression network analysis (WGCNA) to identify key gene modules and potential therapeutic targets. An MPTP-induced PD mouse model was established, and spinal cord transcriptome sequencing was conducted to screen differentially expressed genes (DEGs). Functional enrichment analysis, WGCNA for phenotype-correlated modules, and protein-protein interaction analysis were subsequently conducted to identify key genes. In total, 3473 DEGs were identified (1775 upregulated, 1698 downregulated). Downregulated genes were predominantly enriched in pathways related to oxidative phosphorylation and post-transcriptional regulation, whereas upregulated genes were associated with glutamatergic synapses, axonogenesis, and negative regulation of neurogenesis. Among the five co-expression modules, the brown and yellow modules were most strongly correlated with the PD phenotype, enriched in calcium signaling, inflammation, and spliceosome pathways. Key genes like Akt1, Nlrp3, Tgfb1, Lingo1, and Olig2 were upregulated, whereas Vps35 and Omg were downregulated. This study characterizes the spinal transcriptome of PD mice, suggesting that dysregulated post-transcriptional processes, abnormal oxidative phosphorylation, glutamatergic excitotoxicity, and neuroinflammation may be potential candidate mechanisms and vital involved factors in spinal cord degeneration. These findings provide novel insights into the pathological mechanisms of spinal cord degeneration in PD and lay a foundation for targeted therapy, deserving further investigation.