Transcriptome Sequencing Reveals Molecular Characteristics of Spinal Cord Degeneration in MPTP-Induced Parkinson’s Disease Mice

Abstract

Simple Summary Parkinson’s disease (PD) is the second most common neurodegenerative disorder globally. Its pathological lesions are not restricted to dopaminergic neurons in the substantia nigra but also involve distal tissues such as the spinal cord. However, the molecular mechanisms of spinal cord degeneration remain unclear. This study used a mouse model of PD to investigate the genes that are upregulated or downregulated in the spinal cord. We identified over 3400 differentially expressed genes. Among these, some genes are responsible for regulating cellular energy production, while others are involved in synaptic transmission, axonal growth, and neuroinflammation. Through our analysis of the interactions among these genes, we identified that issues related to dysregulated post-transcriptional processes, abnormal oxidative phosphorylation, glutamatergic excitotoxicity, and neuroinflammation may be potential candidate mechanisms and vital involved factors in spinal cord degeneration of PD. Notably, several potential key genes emerged: some genes were found to be upregulated, indicating heightened neuroinflammation and disrupted neuronal repair, whereas others were downregulated, suggesting impaired energy balance and a loss of the protective myelin sheath surrounding axons. This work broadens our understanding of PD beyond the brain, and provides new insight for developing treatments to alleviate spinal cord degeneration and improve patients’ quality of life.