Inflammatory cascades mediate synapse elimination in spinal cord compression.

Area of Science:

• Neuroscience
• Immunology
• Genetics

Background:

• Cervical compressive myelopathy (CCM) involves spinal cord compression due to spondylosis and ligament ossification.
• Tip-toe walking (twy) mice model spontaneous CCM, showing neuronal loss via apoptosis, but underlying mechanisms require further elucidation.
• Understanding CCM pathophysiology is crucial for developing effective treatments.

Purpose of the Study:

• To investigate the pathophysiology of CCM by analyzing gene expression in compressed spinal cords of twy mice.
• To correlate transcriptome data with physical and histological findings in this animal model.
• To identify molecular mechanisms driving neurodegeneration in CCM.

Main Methods:

• Magnetic resonance imaging (MRI) classified twy mice into severe (S) and mild (M) compression groups.
• Transcriptome analysis utilized microarray and RT-PCR.
• Immunohistology, immuno-electron microscopy, and motor function tests (Rotarod, stride length) were employed.

Main Results:

• Severe compression correlated with spinal canal stenosis and reduced motor function.
• Microarray identified 215 differentially expressed genes, with inflammation-related pathways upregulated in the S group.
• M1 macrophage-dominant inflammation, Cyr61 upregulation, and increased C1q were observed in the S group, alongside microglia/macrophages eliminating synaptic terminals.

Conclusions:

• Detailed pathophysiology of the inflammatory response in CCM was elucidated using the twy mouse model.
• Complement-mediated synapse elimination is identified as a central mechanism in CCM neurodegeneration.
• Findings provide insights into molecular pathways involved in spinal cord compression injury.